Analysis in progress
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complete
This report is still being assembled — sections appear as each stage finishes. It isn't final yet.
Final classification
VUS
c.290A>T

No ACMG/AMP criteria could be met or ruled out for NM_000077.5:c.290A>T due to a critical normalization failure during case preparation: VariantValidator was unavailable and the gene, genomic coordinates, protein consequence, and all downstream evidence sources (gnomAD v2.1/v4.1, ClinVar, REVEL, BayesDel, SpliceAI, COSMIC, OncoKB, Hotspots, literature) could not be resolved. The variant cannot be classified and requires complete re-analysis when normalization services are available.

Gene
N/A
Transcript
N/A
HGVS · transcript:coding
NM_000077.5:c.290A>T
Consequence
N/A
GRCh38
N/A
GRCh37
N/A
Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: none; combination = no applied criteria, which maps to VUS.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: none; combination = no applied criteria, which maps to VUS.
Classification rationale
VUS
c.290A>T

No ACMG/AMP criteria could be met or ruled out for NM_000077.5:c.290A>T due to a critical normalization failure during case preparation: VariantValidator was unavailable and the gene, genomic coordinates, protein consequence, and all downstream evidence sources (gnomAD v2.1/v4.1, ClinVar, REVEL, BayesDel, SpliceAI, COSMIC, OncoKB, Hotspots, literature) could not be resolved. The variant cannot be classified and requires complete re-analysis when normalization services are available.

Applied criteria · 0 applied · 24 assessed
Applied · 0

No criteria were applied for this variant.

Assessed · not applied
Pathogenic
PVS1 Gene could not be resolved during normalization (VariantValidator unavailable); loss-of-function mechanism eligibility and variant class (nonsense/frameshift/canonical splice) could not be determined.
PS1 No ClinVar data available to identify a known pathogenic variant with the same amino acid change; protein consequence could not be resolved during normalization.
PS2 No literature or database evidence of de novo occurrence for this variant was identified; no publications were retrieved for review.
PS3 No functional studies were identified for this variant; no publications, OncoKB, or ClinVar functional evidence available.
PS4 No prevalence or case-control data available; no ClinVar submissions, no publications, and no cohort data retrieved.
PM1 Gene and protein domain architecture could not be resolved; the variant's location relative to known mutational hotspots or critical functional domains is unknown.
PM2 gnomAD v2.1 and v4.1 queries failed because normalization did not resolve genomic coordinates.
PM5 Protein residue context could not be determined; automatic PM5 candidate harvesting was skipped because classic same-residue missense semantics could not be confirmed.
PM6 No de novo reports (with or without paternity confirmation) were identified for this variant in any database or publication source.
PP1 No cosegregation data available; no family studies or pedigrees identified for this variant.
PP2 Cannot assess whether this is a missense variant in a gene with a low rate of benign missense variation — gene not identified and HCI prior score unavailable.
PP3 No in silico scores available: REVEL, BayesDel, SpliceAI, and HCI prior all failed or were skipped because genomic coordinates could not be resolved.
PP4 No phenotype data available; no patient descriptions, clinical presentations, or disease associations could be evaluated.
PP5 No ClinVar submissions and no publications reporting this variant as pathogenic from a reputable source.
Benign
BA1 Population allele frequency cannot be determined; gnomAD v2.1 and v4.1 queries failed due to normalization failure.
BS1 Population allele frequency cannot be determined; gnomAD v2.1 and v4.1 queries failed due to normalization failure.
BS2 No data on observation in healthy adult individuals; no cohort or control data available.
BS3 No functional studies identified showing no deleterious effect; no publications, OncoKB, or functional assay data available.
BS4 No segregation data available to evaluate lack of cosegregation with disease.
BP1 Cannot determine if this is a missense variant in a gene where primarily truncating variants cause disease; gene identity and disease mechanism unknown.
BP2 No data on observation in trans with a known pathogenic variant; no phase or genotype data available.
BP4 No in silico scores available: REVEL, BayesDel, and SpliceAI all failed or were skipped because genomic coordinates and gene could not be resolved.
BP5 No data available on cases where this variant is found with an alternate molecular cause for the phenotype.
BP6 No ClinVar submissions or publications reporting this variant as benign from a reputable source.
N/A · 4 PM3 · PM4 · BP3 · BP7
Research & evidence
Population frequency
v4.1
This variant is absent from gnomAD v4.1.
v2.1
This variant is absent from gnomAD v2.1.
🇨🇦 CA
This variant is absent from gnomAD-Canada.
Allele frequency by ancestry
three datasets · side by side
gnomAD Canada 🇨🇦
Absent · 0 / ?
0 hom
Not observed in any ancestry group.
ClinVar No data
No ClinVar submissions were recorded for this variant.
In silico No data
No in-silico prediction was recorded for this variant.
Functional No data
No calibrated functional assay or RNA evidence was identified for this variant.
Somatic evidence
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant cancer hotspot.
Sources & reference links

No sources recorded.