rs370981751
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_013266.4(CTNNA3):c.1120C>T(p.Arg374Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000616 in 1,607,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R374H) has been classified as Uncertain significance.
Frequency
Consequence
NM_013266.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.1120C>T | p.Arg374Cys | missense_variant | 8/18 | ENST00000433211.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNA3 | ENST00000433211.7 | c.1120C>T | p.Arg374Cys | missense_variant | 8/18 | 1 | NM_013266.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151956Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247634Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133912
GnomAD4 exome AF: 0.0000611 AC: 89AN: 1455686Hom.: 0 Cov.: 29 AF XY: 0.0000497 AC XY: 36AN XY: 724330
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152074Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.1120C>T (p.R374C) alteration is located in exon 8 (coding exon 7) of the CTNNA3 gene. This alteration results from a C to T substitution at nucleotide position 1120, causing the arginine (R) at amino acid position 374 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Arrhythmogenic right ventricular dysplasia 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 19, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CTNNA3 protein function. ClinVar contains an entry for this variant (Variation ID: 409012). This variant has not been reported in the literature in individuals affected with CTNNA3-related conditions. This variant is present in population databases (rs370981751, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 374 of the CTNNA3 protein (p.Arg374Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at