About the gene
No gene-level summary was recorded for this case.
Previous versions
Classification
Uncertain significance
Variant description:
The NM_001202543.1:c.*31777C>T variant could not be checked in COSMIC. Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 0
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
VUS: no adjudicated criterion was applied, so no generic ACMG/AMP pathogenic or benign combination rule is satisfied.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
No screenshot for this evidence
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
No listed criterion applied
gnomAD-Canada ↗
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
No screenshot for this evidence
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
No screenshot for this evidence
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 0 met · 0 not met · 17 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
All three requested criteria are not applicable because the submitted variant is a 3' UTR single-nucleotide substitution, whereas PVS1, PM4, and BP3 each require different variant classes explicitly named in their governing definitions.
None of PS2, PM6, PP1, or BS4 can be assessed from the available record because proband, parental, pedigree, phenotype, and segregation data are absent, and variant normalization is unresolved.
No criteria match.
Not assessed · 17 · no assessment recorded
PS2 ACMG_2015Not assessed: no proband, family-history, or confirmed maternity-and-paternity results are available to establish a de novo occurrence. Details ▾Hide ▴
Reasoning
PS2 cannot be assessed because the case contains no proband phenotype or family-history evidence and no parental maternity and paternity testing results. The available case record also has unresolved variant normalization, with no gene or genomic coordinates, so no patient-level de novo observation can be verified.
Rule
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
Evidence considered
- The case record provides no proband clinical phenotype, family history, or parental genotype results.
- Variant normalization is unresolved: the record contains no gene, genomic coordinates, or validated transcript consequence.
Still missing
- Documented disease phenotype in the proband
- Documented absence of family history
- Parental testing confirming both maternity and paternity
- Resolved variant identity and gene context
PS3 ACMG_2015Not assessed: no variant-specific validated functional assay evidence was available, and normalization failed because the coordinate was outside the reference-sequence bounds. Details ▾Hide ▴
Reasoning
PS3 cannot be assessed from the available evidence. The case has no gene or normalized genomic consequence because the submitted coordinate was reported outside the reference-sequence bounds, and no variant-specific validated in vitro or in vivo functional study, assay result, control set, or publication was available in the functional evidence materials. Therefore, there is no auditable evidence that this variant produces a damaging effect on the gene or gene product.
Rule
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
Evidence considered
- The functional evidence bundle contained no gene, normalized coordinates, functional publications, or extracted functional findings.
- prefetch.json reports that the submitted coordinate was outside the bounds of the reference sequence and that normalization was incomplete.
Still missing
- Resolve the HGVS coordinate and gene/transcript identity.
- Obtain variant-specific in vitro or in vivo functional evidence with assay controls and biological-relevance context.
PS4 ACMG_2015Not assessed: no variant-specific case-control prevalence, odds ratio, relative risk, or confidence interval is available for comparison with the PS4 rule. Details ▾Hide ▴
Reasoning
Not assessed. No case-control study, affected-individual prevalence, control prevalence, relative risk, odds ratio, or confidence interval is available. Variant normalization failed because the coordinate was outside the reference sequence, so the gene and genomic coordinates required to retrieve variant-specific case-control evidence are unresolved.
Rule
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
Evidence considered
- The case evidence has no case-control study or variant-specific prevalence data.
- Normalization reported that the coordinate was outside the bounds of the reference sequence; gene and genomic coordinates remained unresolved.
Still missing
- Resolve the variant's gene and genomic coordinates.
- Obtain variant-specific affected-case and control counts or a reported relative risk/odds ratio with its confidence interval.
PM2 ACMGNot assessed: no gnomAD allele frequency is available to compare with the generic PM2 threshold of <=0.0001. Details ▾Hide ▴
Reasoning
Not assessed: no usable population-frequency record is available. Variant normalization failed for NM_001202543.1:c.*31777C>T, leaving no genomic coordinates and no GNOMAD_V2_1, GNOMAD_V2_1_NON_CANCER, GNOMAD_V3_1_NON_CANCER, or GNOMAD_V4_1 allele-frequency data to determine absence or an extremely low frequency.
Rule
PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
Evidence considered
- The consolidated evidence bundle reports variant-normalization failure and contains empty gnomAD results, so absence or extremely low population frequency cannot be assessed.
- Generic PM2 calibration threshold supplied for this case: allele frequency <= 0.0001.
Still missing
- Resolve the HGVS variant to genomic coordinates.
- Obtain applicable gnomAD allele counts and frequencies, including non-cancer or exome-only subsets if required by a governing specification.
- Determine whether the disorder is recessive before interpreting an extremely low frequency as PM2 evidence.
PM3 ACMG_2015Not assessed: no gene, inheritance mode, pathogenic partner, affected-proband observation, or parental/offspring phase testing is available. Details ▾Hide ▴
Reasoning
PM3 cannot be assessed because the variant could not be normalized to a gene or disease context, and the available case evidence contains no affected-proband observations, pathogenic allele, parental or offspring testing, or phase information establishing that this variant is in trans with a pathogenic variant. Recessive inheritance applicability is therefore unresolved.
Rule
For recessive disorders, detected in trans with a pathogenic variant...This requires testing of parents (or offspring) to determine phase.
Evidence considered
- The case summary reports gene as empty, no normalized genomic coordinates, no disease context, and no literature PMIDs.
- The evidence and literature files contain no observations of an affected proband, pathogenic allele, parental testing, offspring testing, or cis/trans phase.
- The supplied governing rule requires a recessive disorder and detection in trans with a pathogenic variant, with parental or offspring testing to determine phase.
Still missing
- Resolve the variant to a gene and associated disorder.
- Establish whether the disorder is recessive.
- Obtain affected-proband observations and identify any pathogenic allele in the same individual.
- Obtain parental or offspring testing to establish phase.
- Confirm that the alleles are in trans.
PM6 ACMG_2015Not assessed: no patient-level de novo observation or parental testing is documented for an assumed de novo classification. Details ▾Hide ▴
Reasoning
PM6 cannot be assessed because the case contains no documented patient-level de novo finding and no parental testing results. In particular, there is no evidence that the variant was assumed de novo without confirmation of maternity and paternity.
Rule
Assumed de novo, but without confirmation of paternity and maternity.
Evidence considered
- The case record contains no proband or parental genotype results and no clinical report describing a de novo occurrence.
- Variant normalization is unresolved, preventing verification that any reported parental result corresponds to this variant.
Still missing
- Documented disease phenotype in the proband
- Variant genotypes in the proband and both parents
- Evidence supporting de novo status
- Resolved variant identity and gene context
PP1 ACMG_2015Not assessed: no affected relatives, segregation results, informative meioses, or definitive gene-disease relationship are documented. Details ▾Hide ▴
Reasoning
PP1 cannot be assessed because no affected family members, family structure, segregation results, or number of informative meioses are documented. The record also does not identify the gene or establish that it is definitively known to cause the disease.
Rule
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
Evidence considered
- The case record provides no pedigree, affected-family-member data, segregation testing, or informative-meiosis count.
- The gene field is empty, so the required definitive gene-disease relationship cannot be verified.
Still missing
- Identified disease and definitive gene-disease relationship
- Pedigree with affected and unaffected relatives
- Genotypes and phenotypes for informative family members
- Number of informative meioses
PP4 ACMG_2015Not assessed: no patient phenotype or family history is available to determine whether the presentation is highly specific for a single-gene disease. Details ▾Hide ▴
Reasoning
Not assessed. The case contains no patient phenotype, family history, disease diagnosis, or single-gene-etiology evidence that would permit evaluation of phenotype specificity. The unresolved gene and variant normalization further prevent disease-specific assessment.
Rule
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
Evidence considered
- The case summary contains no phenotype or family-history data.
- The gene is unresolved after incomplete variant normalization.
Still missing
- Obtain the patient's confirmed phenotype and relevant family history.
- Resolve the gene and establish the associated disease context and etiologic specificity.
PP5 ACMG_2015Not assessed: no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification is available for this unresolved variant. Details ▾Hide ▴
Reasoning
Not assessed. No exact-variant ClinVar expert-panel classification was retrieved. ClinVar lookup was skipped because normalization did not resolve a gene or coordinates; therefore there is no qualifying Pathogenic or Likely pathogenic expert-panel assertion to apply PP5, and no basis to conclude that the criterion is absent.
Rule
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Evidence considered
- ClinVar retrieval was skipped because variant normalization produced no gene or genomic coordinates.
- No exact-variant expert-panel classification is present in the available case evidence.
Still missing
- Resolve the variant identity and retrieve its exact-variant ClinVar submissions and review status.
- Confirm whether an expert panel classified the exact variant as Pathogenic or Likely pathogenic.
BA1 ACMGNot assessed: no gnomAD allele frequency is available to compare with the generic BA1 threshold of >=0.05. Details ▾Hide ▴
Reasoning
Not assessed: no usable population-frequency record is available. Variant normalization failed for NM_001202543.1:c.*31777C>T, leaving no genomic coordinates and no GNOMAD_V2_1, GNOMAD_V2_1_NON_CANCER, GNOMAD_V3_1_NON_CANCER, or GNOMAD_V4_1 allele-frequency data to compare with the generic BA1 threshold of >= 0.05.
Rule
BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
Evidence considered
- The consolidated evidence bundle reports variant-normalization failure and contains empty gnomAD results, so no population frequency can be assessed.
- Generic BA1 calibration threshold supplied for this case: allele frequency >= 0.05.
Still missing
- Resolve the HGVS variant to genomic coordinates.
- Obtain applicable gnomAD allele counts and frequencies, including non-cancer or exome-only subsets if required by a governing specification.
BS1 ACMGNot assessed: no gnomAD allele frequency is available to compare with the generic BS1 threshold of >=0.01. Details ▾Hide ▴
Reasoning
Not assessed: no usable population-frequency record is available. Variant normalization failed for NM_001202543.1:c.*31777C>T, leaving no genomic coordinates and no GNOMAD_V2_1, GNOMAD_V2_1_NON_CANCER, GNOMAD_V3_1_NON_CANCER, or GNOMAD_V4_1 allele-frequency data to compare with the generic BS1 threshold of >= 0.01.
Rule
Allele frequency is greater than expected for disorder. ... BS1 (strong): >= 0.01 — Generic SVI default; per-gene derivation preferred (Whiffin et al. 2017) (PMID:28518168)
Evidence considered
- The consolidated evidence bundle reports variant-normalization failure and contains empty gnomAD results, so observed population frequency cannot be compared with expected frequency for the disorder.
- Generic BS1 calibration threshold supplied for this case: allele frequency >= 0.01; per-gene derivation is preferred.
Still missing
- Resolve the HGVS variant to genomic coordinates.
- Establish the expected disease allele frequency using disease prevalence, penetrance, inheritance, and applicable population data.
- Obtain applicable gnomAD allele counts and frequencies, including non-cancer or exome-only subsets if required by a governing specification.
BS2 ACMG_2015Not assessed: no healthy-adult genotype observation is available for the required homozygous, heterozygous, or hemizygous assessment. Details ▾Hide ▴
Reasoning
Not assessed: no individual-level population observation or phenotype/inheritance context is available. Variant normalization failed for NM_001202543.1:c.*31777C>T, and the case contains no usable evidence establishing observation in a healthy adult as a homozygote, heterozygote, or hemizygote for a fully penetrant early-onset disorder.
Rule
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Evidence considered
- The consolidated evidence bundle contains no individual-level population observations, genotype counts, or disease-model information usable for BS2.
Still missing
- Resolve the HGVS variant to genomic coordinates.
- Obtain reliable individual-level observations and confirm genotype state, health status, age, inheritance model, and expected penetrance.
BS3 ACMG_2015Not assessed: no variant-specific validated functional assay evidence was available, and normalization failed because the coordinate was outside the reference-sequence bounds. Details ▾Hide ▴
Reasoning
BS3 cannot be assessed from the available evidence. The case has no gene or normalized genomic consequence because the submitted coordinate was reported outside the reference-sequence bounds, and no variant-specific validated in vitro or in vivo functional study, assay result, control set, or publication was available in the functional evidence materials. Therefore, there is no auditable evidence that this variant has no damaging effect on protein function or splicing.
Rule
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
Evidence considered
- The functional evidence bundle contained no gene, normalized coordinates, functional publications, or extracted functional findings.
- prefetch.json reports that the submitted coordinate was outside the bounds of the reference sequence and that normalization was incomplete.
Still missing
- Resolve the HGVS coordinate and gene/transcript identity.
- Obtain variant-specific in vitro or in vivo functional evidence with assay controls and biological-relevance context.
BS4 ACMG_2015Not assessed: no affected-family genotypes or phenotype/genotype discordance are documented to demonstrate lack of segregation. Details ▾Hide ▴
Reasoning
BS4 cannot be assessed because no affected family members, family pedigree, variant genotypes, or phenotype/genotype discordance are documented. Therefore, lack of segregation cannot be distinguished from absent testing, incomplete ascertainment, or phenocopy.
Rule
Lack of segregation in affected members of a family.
Evidence considered
- The case record contains no pedigree, affected-relative testing, or family-level phenotype/genotype comparison.
- Without affected-relative data, lack of segregation and possible phenocopy cannot be evaluated.
Still missing
- Pedigree identifying affected family members
- Variant testing results for affected relatives
- Phenotype details for each affected relative
- Assessment of possible phenocopies or multiple pathogenic variants
BP2 ACMG_2015Not assessed: no pathogenic partner or phase data show the variant in trans for a fully penetrant dominant disorder or in cis in any inheritance pattern. Details ▾Hide ▴
Reasoning
BP2 cannot be assessed because the available case evidence contains no affected-proband or family observations showing this variant in trans with a pathogenic variant in a fully penetrant dominant disorder, or in cis with a pathogenic variant in any inheritance pattern. The gene, disorder, inheritance model, pathogenic partner, and phase are unresolved.
Rule
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
Evidence considered
- The case summary reports gene as empty, no normalized genomic coordinates, no disease context, and no literature PMIDs.
- The evidence and literature files contain no observations establishing a pathogenic variant in cis or trans with the queried variant.
- The supplied governing rule requires either trans observation with a pathogenic variant in a fully penetrant dominant gene/disorder or cis observation with a pathogenic variant in any inheritance pattern.
Still missing
- Resolve the variant to a gene and associated disorder.
- Establish the inheritance model and, if dominant, whether the disorder is fully penetrant.
- Identify any pathogenic variant in the same individual or family.
- Obtain testing that establishes cis or trans phase.
BP5 ACMG_2015Not assessed: no case evidence shows an alternate molecular basis for the disease in a patient carrying this unresolved variant. Details ▾Hide ▴
Reasoning
Not assessed. No case-level evidence identifies an alternate molecular basis for the disease, and no patient diagnosis or phenotype is available to establish that context. The unresolved variant identity also prevents targeted review of relevant case reports.
Rule
Variant found in a case with an alternate molecular basis for disease.
Evidence considered
- No case report or clinical record in the available evidence documents an alternate molecular basis for disease.
- The variant could not be normalized to a gene or genomic coordinate.
Still missing
- Obtain the patient's disease diagnosis and molecular workup.
- Determine whether an independently established alternate pathogenic molecular cause exists in the same case.
BP6 ACMG_2015Not assessed: no exact-variant ClinVar expert-panel Benign or Likely benign classification is available for this unresolved variant. Details ▾Hide ▴
Reasoning
Not assessed. No exact-variant ClinVar expert-panel classification was retrieved. ClinVar lookup was skipped because normalization did not resolve a gene or coordinates; therefore there is no qualifying Benign or Likely benign expert-panel assertion to apply BP6, and no basis to conclude that the criterion is absent.
Rule
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Evidence considered
- ClinVar retrieval was skipped because variant normalization produced no gene or genomic coordinates.
- No exact-variant expert-panel classification is present in the available case evidence.
Still missing
- Resolve the variant identity and retrieve its exact-variant ClinVar submissions and review status.
- Confirm whether an expert panel classified the exact variant as Benign or Likely benign.
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANot applicable: c.*31777C>T is a 3' UTR SNV, not one of the null-variant types named by the PVS1 rule. Details ▾Hide ▴
Reasoning
The submitted variant is NM_001202543.1:c.*31777C>T, a 3' UTR star-coordinate SNV. It is not a nonsense variant, frameshift, canonical +/-1 or 2 splice-site variant, initiation-codon variant, or single-/multi-exon deletion, so it lies outside the variant types named by PVS1. Gene-level loss-of-function mechanism and transcript normalization could not be resolved because validation reported that the coordinate was outside the reference-sequence bounds, but that unresolved context does not make this 3' UTR SNV a PVS1 null-variant type.
Rule
PVS1: Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease.
Evidence considered
- The case variant is recorded as NM_001202543.1:c.*31777C>T; the c.* notation places it in the 3' UTR and identifies a single-nucleotide substitution.
- VariantValidator reported that the coordinate was outside the reference-sequence bounds, and no gene, protein consequence, exon, or canonical-splice annotation was available.
- Under the generic PVS1 definition, the named null-variant classes are nonsense, frameshift, canonical +/-1 or 2 splice sites, initiation codon, and single- or multi-exon deletion; this variant is none of those classes.
Still missing
- Gene identity and transcript normalization could not be confirmed because validation reported that the coordinate was outside the reference-sequence bounds.
PS1 N/ANot applicable: c.*31777C>T is a downstream-of-stop coordinate, not an amino-acid-changing missense variant eligible for same-amino-acid comparison. Details ▾Hide ▴
Reasoning
PS1 applies to a missense change producing the same amino acid change as a previously established pathogenic variant. The submitted variant is NM_001202543.1:c.*31777C>T, a downstream-of-stop c.* coordinate rather than an amino-acid-changing missense variant; no amino-acid change can therefore be evaluated under PS1.
Rule
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
Evidence considered
- Case variant input: NM_001202543.1:c.*31777C>T; the c.* notation places the variant downstream of the coding stop and provides no amino-acid change.
PM1 N/ANot applicable: c.*31777C>T lies downstream of the coding sequence, so no codon, protein residue, hotspot, or functional-domain location is available. Details ▾Hide ▴
Reasoning
PM1 applies to a variant located in a mutational hotspot or critical and well-established functional domain. The submitted c.* coordinate is downstream of the coding sequence rather than a codon or protein residue, so residue-domain or hotspot assessment under PM1 is not applicable.
Rule
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
Evidence considered
- Case variant input: NM_001202543.1:c.*31777C>T; the c.* coordinate is downstream of the coding stop and cannot be mapped to a protein residue or codon.
PM4 N/ANot applicable: c.*31777C>T is a 3' UTR SNV with no established protein-length change, not an in-frame indel or stop-loss variant. Details ▾Hide ▴
Reasoning
The submitted variant is NM_001202543.1:c.*31777C>T, a 3' UTR single-nucleotide substitution. It is not an in-frame insertion, in-frame deletion, or stop-loss variant, and no protein-length change is established; therefore it lies outside the variant types named by PM4.
Rule
PM4: Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.
Evidence considered
- The case variant is recorded as NM_001202543.1:c.*31777C>T, which is a single-nucleotide substitution in the 3' UTR rather than an in-frame coding insertion, deletion, or stop-loss change.
- No protein consequence or protein-length change was available because normalization failed.
Still missing
- Transcript and protein consequence could not be normalized because validation reported that the coordinate was outside the reference-sequence bounds.
PM5 N/ANot applicable: c.*31777C>T is downstream of the coding sequence and specifies no amino-acid residue for alternate-pathogenic-change comparison. Details ▾Hide ▴
Reasoning
PM5 applies to a novel missense change at an amino-acid residue where a different pathogenic missense change has been observed. The submitted c.* coordinate is downstream of the coding sequence and does not specify an amino-acid residue, so same-residue comparison is not applicable.
Rule
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
Evidence considered
- Case variant input: NM_001202543.1:c.*31777C>T; no protein consequence or amino-acid residue is defined.
PP2 N/ANot applicable: c.*31777C>T is not a missense variant, and the case provides no gene for evaluating missense constraint or disease mechanism. Details ▾Hide ▴
Reasoning
PP2 applies to a missense variant in a gene with a low rate of benign missense variation where missense variants are a common disease mechanism. The submitted c.* coordinate is not a missense variant, and the case does not identify a gene for gene-level assessment.
Rule
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Evidence considered
- Case summary identifies the gene as blank and the variant as NM_001202543.1:c.*31777C>T; the coordinate is downstream of the coding stop rather than missense.
PP3 N/ANot applicable: the 3' UTR variant c.*31777C>T is outside the generic PP3 missense and splice-region/intronic computational scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a missense, synonymous, intronic, or splice-region variant covered by the generic PP3 computational paths. Therefore no REVEL or SpliceAI score is evaluated for PP3.
Rule
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region.
- The generic rule limits PP3/BP4 to missense variants or splice-region/intronic variants through the applicable predictor path; a 3' UTR variant is outside that scope, so predictor scores are not needed.
BP1 N/ANot applicable: c.*31777C>T is not a missense variant, and the case provides no gene for assessing whether truncating variants primarily cause disease. Details ▾Hide ▴
Reasoning
BP1 applies to a missense variant in a gene for which primarily truncating variants are known to cause disease. The submitted c.* coordinate is not a missense variant, and the case does not identify a gene for gene-level mechanism assessment.
Rule
Missense variant in a gene for which primarily truncating variants are known to cause disease.
Evidence considered
- Case summary identifies the gene as blank and the variant as NM_001202543.1:c.*31777C>T; the coordinate is downstream of the coding stop rather than missense.
BP3 N/ANot applicable: c.*31777C>T is a 3' UTR SNV, not an in-frame deletion or insertion required for BP3. Details ▾Hide ▴
Reasoning
The submitted variant is NM_001202543.1:c.*31777C>T, a 3' UTR single-nucleotide substitution. It is not an in-frame deletion or insertion, so the BP3 criterion does not apply regardless of whether the surrounding sequence is repetitive or functionally characterized.
Rule
BP3: In frame-deletions/insertions in a repetitive region without a known function.
Evidence considered
- The case variant is recorded as NM_001202543.1:c.*31777C>T, a single-nucleotide substitution rather than an in-frame deletion or insertion.
- No normalized genomic interval or repeat annotation was available because validation reported that the coordinate was outside the reference-sequence bounds.
Still missing
- The repeat-region context could not be evaluated because transcript and genomic normalization failed, but repeat context cannot establish BP3 for this SNV.
BP4 N/ANot applicable: the 3' UTR variant c.*31777C>T is outside the generic BP4 missense and splice-region/intronic computational scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a missense, synonymous, intronic, or splice-region variant covered by the generic BP4 computational paths. Therefore no REVEL or SpliceAI score is evaluated for BP4.
Rule
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region.
- The generic rule limits PP3/BP4 to missense variants or splice-region/intronic variants through the applicable predictor path; a 3' UTR variant is outside that scope, so predictor scores are not needed.
BP7 N/ANot applicable: the 3' UTR variant c.*31777C>T is not a synonymous coding variant within BP7's defined scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a synonymous coding variant, so the generic BP7 rule does not cover it.
Rule
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region, rather than in a coding synonymous position.
Identifiers
- Coding (HGVS c.)
- NM_001202543.1:c.*31777C>T
- Location and type
- unknown
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
No population statements were recorded.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/ANot applicable: the 3' UTR variant c.*31777C>T is outside the generic PP3 missense and splice-region/intronic computational scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a missense, synonymous, intronic, or splice-region variant covered by the generic PP3 computational paths. Therefore no REVEL or SpliceAI score is evaluated for PP3.
Rule
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region.
- The generic rule limits PP3/BP4 to missense variants or splice-region/intronic variants through the applicable predictor path; a 3' UTR variant is outside that scope, so predictor scores are not needed.
BP4 N/ANot applicable: the 3' UTR variant c.*31777C>T is outside the generic BP4 missense and splice-region/intronic computational scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a missense, synonymous, intronic, or splice-region variant covered by the generic BP4 computational paths. Therefore no REVEL or SpliceAI score is evaluated for BP4.
Rule
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc). ... PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region.
- The generic rule limits PP3/BP4 to missense variants or splice-region/intronic variants through the applicable predictor path; a 3' UTR variant is outside that scope, so predictor scores are not needed.
BP7 N/ANot applicable: the 3' UTR variant c.*31777C>T is not a synonymous coding variant within BP7's defined scope. Details ▾Hide ▴
Reasoning
Not applicable: NM_001202543.1:c.*31777C>T is a 3' untranslated-region variant, not a synonymous coding variant, so the generic BP7 rule does not cover it.
Rule
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Evidence considered
- Variant HGVS position c.*31777 places c.31777C>T in the transcript's 3' untranslated region, rather than in a coding synonymous position.
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.