rs970349800

Variant names:

• chr10-67180460-T-C
• rs970349800
• NM_013266.4:c.904A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013266.4(CTNNA3):​c.904A>G​(p.Lys302Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNA3 NM_013266.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

Genes affected

CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12491462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.904A>G	p.Lys302Glu	missense_variant	Exon 7 of 18	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.904A>G	p.Lys302Glu	missense_variant	Exon 7 of 18	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 13 Uncertain:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 302 of the CTNNA3 protein (p.Lys302Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTNNA3-related conditions. ClinVar contains an entry for this variant (Variation ID: 541661). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.85	N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	2.2	N;.
REVEL	Benign	0.045
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;.
Vest4		0.25
MVP		0.28
MPC		0.098
ClinPred		0.81	D
GERP RS		4.7
Varity_R		0.075
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs970349800; hg19: chr10-68940218;