rs2456751

Variant names:

• chr10-66405295-T-C
• rs2456751
• NM_013266.4:c.1532-25943A>G

Variant summary

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

The NM_013266.4(CTNNA3):​c.1532-25943A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,926 control chromosomes in the GnomAD database, including 31,725 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 0.63 (31725 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1532-25943A>G		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.1532-25943A>G		intron_variant	Intron 11 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95469 AN: 151808 Hom.: 31676 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.629 AC: 95577 AN: 151926 Hom.: 31725 Cov.: 32 AF XY: 0.630 AC XY: 46785 AN XY: 74208

African (AFR) AF: 0.823 AC: 34103 AN: 41452

American (AMR) AF: 0.578 AC: 8809 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3472

East Asian (EAS) AF: 0.885 AC: 4536 AN: 5126

South Asian (SAS) AF: 0.809 AC: 3897 AN: 4818

European-Finnish (FIN) AF: 0.467 AC: 4928 AN: 10546

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35168 AN: 67950

Other (OTH) AF: 0.634 AC: 1337 AN: 2110

Alfa AF: 0.562 Hom.: 3160

Bravo AF: 0.641

Asia WGS AF: 0.854 AC: 2968 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.66
PhyloP100		-0.82
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: rs2456751; hg19: chr10-68165053;