rs2894016

chr10-66664632-A-Cchr10-66664632-A-Gchr10-66664632-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):c.1282-42848T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,536 control chromosomes in the GnomAD database, including 33,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33324 hom., cov: 29)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1282-42848T>G		intron_variant		ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1282-42848T>G		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99159 AN: 151418 Hom.: 33295 Cov.: 29

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.628

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.655 AC: 99237 AN: 151536 Hom.: 33324 Cov.: 29 AF XY: 0.657 AC XY: 48603 AN XY: 73998

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.631

Alfa AF: 0.467 Hom.: 1178

Bravo AF: 0.664

Asia WGS AF: 0.796 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.2
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2894016; hg19: chr10-68424390;