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NM_000546.6:c.1100-3C>T
Generic ACMG/AMP 2015 with ClinGen SVI recommendations
0%
complete
Final classification
VUS
c.1100-3C>T
unknown
This variant

The gene-level disease mechanism and clinical context for NM_000546.6:c.1100-3C>T remain unavailable because the submitted transcript variant could not be normalized.

Transcript
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HGVS · transcript:coding
NM_000546.6:c.1100-3C>T
GRCh38
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GRCh37
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VUS: no adjudicated criteria were met or applied, so the generic ACMG/AMP 2015 combination thresholds for pathogenic or benign classification were not satisfied.
Classification rationale
VUS
c.1100-3C>T unknown

Under generic ACMG/AMP rules, PVS1 is not applicable because the submitted c.1100-3 substitution is outside the named canonical ±1/±2 splice-site and other null-variant classes; normalization and gene-level LOF context are unresolved. PM4 and BP3 are not applicable because the submitted variant is an intronic single-nucleotide substitution, not an in-frame insertion/deletion or stop-loss variant. All five requested criteria are not_assessed because the variant could not be normalized and the case evidence lacks the clinical, case-control, alternate-molecular-basis, and exact-variant ClinVar expert-panel data required for adjudication. PP3 and BP4 are within scope only through the intronic SpliceAI path, but the variant could not be normalized and no SpliceAI score is available. BP7 is outside scope because the submitted variant is intronic rather than synonymous. All four population criteria are not assessed because the submitted intronic HGVS expression could not be normalized to a gene and genomic coordinate, leaving no usable population-frequency or healthy-adult observation data. No criterion is inferred from another source's classification, and no VCEP-specific population rule applies because the case is governed by generic ACMG/AMP rules.

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.
Applied criteria · 0 applied · 19 assessed
MetEvidence satisfies this criterion.
Not metEvaluated against available evidence; threshold not reached.
Not assessedApplies in principle, but no evidence was found to evaluate it.
N/ADoesn't apply to this variant type.
Applied · 0

No criteria were applied for this variant.

Assessed · not applied · 0 not met · 19 not assessed
Pathogenic
PS2 Not assessed: no documented proband, family-history status, or confirmed maternity and paternity is available to evaluate de novo occurrence.
PS3 Not assessed: no validated in vitro or in vivo functional assay evidence was available, and the variant could not be normalized for targeted evidence retrieval.
PS4 Not assessed: no case-control odds ratio or relative risk, confidence interval, or affected-versus-control prevalence data are available.
PM2 Not assessed: no applicable population observation is available to test the <=0.0001 PM2 threshold or establish absence from controls.
PM3 Not assessed: no affected-proband observation, pathogenic allele, or parent/offspring phase testing establishes a PM3-relevant variant in trans.
PM6 Not assessed: no proband de novo observation or parental testing status is documented for the variant.
PP1 Not assessed: no affected relatives, matching genotypes, phenotype data, or informative meioses are documented for segregation analysis.
PP3 Not assessed: the applicable intronic SpliceAI path has no score, and transcript validation could not confirm the c.1100-3 location.
PP4 Not assessed: no patient phenotype or family history is provided to establish specificity for a single-gene disease.
PP5 Not assessed: no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification is available.
Benign
BA1 Not assessed: no population allele-frequency observation is available, so comparison with the >=0.05 BA1 threshold is impossible.
BS1 Not assessed: no observed population frequency is available for comparison with the generic BS1 threshold of >=0.01.
BS2 Not assessed: no healthy-adult homozygote, heterozygote, or hemizygote observation is available and penetrance is unresolved.
BS3 Not assessed: no validated in vitro or in vivo functional assay evidence was available, and the variant could not be normalized for targeted evidence retrieval.
BS4 Not assessed: no affected relatives with documented variant status and phenotype are available to evaluate lack of segregation.
BP2 Not assessed: no resolved inheritance mode or documented cis/trans relationship with a pathogenic variant is available for BP2.
BP4 Not assessed: the applicable intronic SpliceAI path has no score, and transcript validation could not confirm the c.1100-3 location.
BP5 Not assessed: no alternate molecular basis for the disease is documented in the available case evidence.
BP6 Not assessed: no exact-variant ClinVar expert-panel Benign or Likely benign classification is available.
N/A · 9 PVS1 · PS1 · PM1 · PM4 · PM5 · PP2 · BP1 · 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.
gnomAD 🇨🇦 ↗
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.