rs2894016

Variant names:

• chr10-66664632-A-C
• rs2894016
• NM_013266.4:c.1282-42848T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-66664632-A-C
• chr10-66664632-A-G
• chr10-66664632-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CTNNA3 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1282-42848T>G		intron_variant	Intron 9 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1282-42848T>G		intron_variant	Intron 9 of 17	1	NM_013266.4	ENSP00000389714.1

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

African (AFR) AF: 0.762 AC: 31504 AN: 41318

American (AMR) AF: 0.643 AC: 9786 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2070 AN: 3464

East Asian (EAS) AF: 0.948 AC: 4843 AN: 5108

South Asian (SAS) AF: 0.663 AC: 3183 AN: 4804

European-Finnish (FIN) AF: 0.612 AC: 6426 AN: 10492

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39350 AN: 67840

Other (OTH) AF: 0.631 AC: 1326 AN: 2100

Alfa AF: 0.488 Hom.: 1385

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
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2894016; hg19: chr10-68424390;