rs28363394
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_001903.5(CTNNA1):c.536C>T(p.Ala179Val) variant causes a missense change. The variant allele was found at a frequency of 0.00202 in 1,613,660 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A179T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001903.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNA1 | NM_001903.5 | c.536C>T | p.Ala179Val | missense_variant | 5/18 | ENST00000302763.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNA1 | ENST00000302763.12 | c.536C>T | p.Ala179Val | missense_variant | 5/18 | 1 | NM_001903.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00146 AC: 222AN: 152008Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00117 AC: 294AN: 251350Hom.: 0 AF XY: 0.00120 AC XY: 163AN XY: 135832
GnomAD4 exome AF: 0.00208 AC: 3038AN: 1461534Hom.: 2 Cov.: 30 AF XY: 0.00206 AC XY: 1501AN XY: 727080
GnomAD4 genome AF: 0.00146 AC: 222AN: 152126Hom.: 1 Cov.: 32 AF XY: 0.00134 AC XY: 100AN XY: 74376
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | CTNNA1: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 17, 2021 | - - |
CTNNA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at