rs1032740164
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_013266.4(CTNNA3):c.1247C>T(p.Ala416Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A416T) has been classified as Uncertain significance.
Frequency
Consequence
NM_013266.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNA3 | NM_013266.4 | c.1247C>T | p.Ala416Val | missense_variant | 9/18 | ENST00000433211.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNA3 | ENST00000433211.7 | c.1247C>T | p.Ala416Val | missense_variant | 9/18 | 1 | NM_013266.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251132Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135706
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727110
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 13 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 26, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2017 | This sequence change replaces alanine with valine at codon 416 of the CTNNA3 protein (p.Ala416Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CTNNA3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at