rs922347

Variant names:

• chr10-66223200-G-A
• rs922347
• NM_013266.4:c.1884+57270C>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.1884+57270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,628 control chromosomes in the GnomAD database, including 22,915 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 0.54 (22915 hom., cov: 30)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1884+57270C>T		intron_variant	Intron 13 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1884+57270C>T		intron_variant	Intron 13 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81872 AN: 151508 Hom.: 22900 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.540 AC: 81910 AN: 151628 Hom.: 22915 Cov.: 30 AF XY: 0.547 AC XY: 40524 AN XY: 74050

African (AFR) AF: 0.373 AC: 15410 AN: 41364

American (AMR) AF: 0.577 AC: 8790 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2836 AN: 5116

South Asian (SAS) AF: 0.691 AC: 3322 AN: 4810

European-Finnish (FIN) AF: 0.655 AC: 6857 AN: 10462

Middle Eastern (MID) AF: 0.621 AC: 180 AN: 290

European-Non Finnish (NFE) AF: 0.598 AC: 40608 AN: 67880

Other (OTH) AF: 0.552 AC: 1161 AN: 2102

Alfa AF: 0.568 Hom.: 5217

Bravo AF: 0.528

Asia WGS AF: 0.586 AC: 2028 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.029
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: rs922347; hg19: chr10-67982958;