rs2456737

Variant names:

• chr10-66395576-A-G
• rs2456737
• NM_013266.4:c.1532-16224T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1532-16224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,900 control chromosomes in the GnomAD database, including 3,971 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 0.20 (3971 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1532-16224T>C		intron_variant	Intron 11 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1532-16224T>C		intron_variant	Intron 11 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31044 AN: 151782 Hom.: 3961 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.205 AC: 31076 AN: 151900 Hom.: 3971 Cov.: 31 AF XY: 0.199 AC XY: 14809 AN XY: 74264

African (AFR) AF: 0.369 AC: 15296 AN: 41422

American (AMR) AF: 0.130 AC: 1985 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.0994 AC: 512 AN: 5150

South Asian (SAS) AF: 0.163 AC: 785 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1311 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9920 AN: 67892

Other (OTH) AF: 0.205 AC: 433 AN: 2108

Alfa AF: 0.162 Hom.: 1647

Bravo AF: 0.210

Asia WGS AF: 0.163 AC: 570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.58
PhyloP100		-0.65
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: rs2456737; hg19: chr10-68155334;