Classification rationale
VUS
No rationale recorded.
Final classification
VUS
CTNNA1
c.*17C>T
p.=
synonymous · exon 18
Gene context
NCBI Gene ↗
OncoKB ↗
CTNNA1 encodes a member of the catenin protein family that plays a central role in cell adhesion by linking cadherins on the cell surface to the actin cytoskeleton; its mechanosensing activity lets cells respond to physical tension and reorganize these connections. Mutations in this gene cause butterfly-shaped pigment dystrophy of the eye. CTNNA1 also acts as a tumor suppressor: its inactivation promotes cellular invasiveness and metastasis, and reduced expression has been observed in several cancers, including bladder cancer, acute myeloid leukemia, and breast cancer.
This variant
This CTNNA1 downstream 3′-UTR synonymous variant occurs in a gene involved in cell adhesion and associated with butterfly-shaped pigment dystrophy and tumor-suppressor function.
VUS: no adjudicated criteria were applied, so generic ACMG/AMP 2015 fallback rules do not meet a definitive classification threshold.
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.
Gene diagram
· NM_001903.5 · variants mapped to exon structure
CTNNA1
NM_001903.5
Fetching transcript structure from UCSC…
Applied criteria · 0 applied · 17 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
· 3 not met · 14 not assessed
Pathogenic
PS2
Not assessed: no proband phenotype, parental genotypes, maternity/paternity confirmation, or documented de novo observation is available.
PS3
Not assessed: no variant-specific functional assay or calibrated PS3 result was reported for CTNNA1 NM_001903.5:c.*17C>T.
PS4
Not assessed: no case-control enrichment, affected-case prevalence, odds ratio, or other variant-specific PS4 metric was available.
PM2
Not met: gnomAD v4.1 allele frequency is 0.000237126, above the generic PM2 threshold of 0.0001.
PM6
Not assessed: the case contains no reported de novo event, affected proband, or parental genotype results, whether or not parentage was confirmed.
PP1
Not assessed: no affected relatives, family genotypes, phenotype concordance, pedigree, or informative meioses are documented.
PP4
Not assessed: no exact-variant proband phenotype or highly specific CTNNA1-related clinical presentation was documented.
PP5
Not assessed: ClinVar has zero expert-panel submissions and its record is a different variant, c.2472C>T rather than c.*17C>T.
Benign
BA1
Not met: the highest reported frequency is 0.00421782, below the generic BA1 threshold of 0.05.
BS1
Not met: the highest robust group-level frequency is 0.00421782, below the generic BS1 threshold of 0.01.
BS2
Not assessed: gnomAD v4.1 has one homozygote, but unaffected-adult status and complete CTNNA1 disease penetrance are unverified.
BS3
Not assessed: no variant-specific functional assay or calibrated BS3 result was reported for CTNNA1 NM_001903.5:c.*17C>T.
BS4
Not assessed: no affected-relative phenotypes, familial genotypes, or reliable non-segregation analysis is available.
BP2
Not assessed: no second variant, affected-proband observation, pedigree, segregation result, or cis/trans phase determination is documented for c.*17C>T.
BP5
Not assessed: no variant-specific co-occurrence, phase, or likelihood-ratio evidence with an explanatory pathogenic variant was available.
BP6
Not assessed: ClinVar provides no exact-variant expert-panel Benign or Likely benign classification for c.*17C>T.
BP7
Not assessed: the variant is synonymous, but SpliceAI returned no calibrated score to establish absence of splice impact.
N/A · 11
PVS1 · PS1 · PM1 · PM3 · PM4 · PM5 · PP2 · PP3 · BP1 · BP3 · BP4
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 0.000237126; MAF= 0.02371%, 379/1598306 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.00400708; MAF= 0.40071%, 299/74618 alleles, homozygotes = 1); grpmax FAF= 0.00363366.
v2.1
This variant is present in gnomAD v2.1 (AF= 0.000416833; MAF= 0.04168%, 113/271092 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00398156; MAF= 0.39816%, 95/23860 alleles, homozygotes = 0); grpmax FAF= 0.00327332.
🇨🇦 CA
Not available in gnomAD-Canada v1.0.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.024%
· 379 / 1,598,306
1 hom · FAF 0.36%
1 hom · FAF 0.36%
African/African American 299 / 74,618 |
0.4% 1 hom |
Remaining individuals 15 / 61,988 |
0.024% |
Admixed American 10 / 59,650 |
0.017% |
European (non-Finnish) 54 / 1,171,510 |
0.0046% |
Ashkenazi Jewish 1 / 29,420 |
0.0034% |
+ 5 not observed (European (Finnish), Amish, East Asian, Middle Eastern, South Asian)
gnomAD v2.1
0.042%
· 113 / 271,092
0 hom · FAF 0.33%
0 hom · FAF 0.33%
African/African American 95 / 23,860 |
0.4% |
Remaining individuals 4 / 6,996 |
0.057% |
Admixed American 6 / 34,918 |
0.017% |
European (non-Finnish) 8 / 125,632 |
0.0064% |
+ 4 not observed (Ashkenazi Jewish, East Asian, European (Finnish), South Asian)
gnomAD Canada 🇨🇦
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
In silico
SpliceAI returned NO scores for this variant, so no SpliceAI-based splice prediction is available. This is missing data, NOT evidence of absent splice impact: it must not be used to support BP4 or to argue against PP3/PVS1. Pangolin scores may be present but are not calibrated for PP3/BP4 here.
Functional
Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. CTNNA1, a cytoplasmic adhesion protein, is infrequently altered in cancer.
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
Triaged references · 6 PMIDs not cited in assessment
20065170 ↗
American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility.
CLINVAR
25394175 ↗
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.
CLINVAR
28492532 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
CLINVAR