chr10-66319415-C-T

Variant names:

• chr10-66319415-C-T
• rs7088181
• NM_013266.4:c.1733-38794G>A

Variant summary

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

The NM_013266.4(CTNNA3):​c.1733-38794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,972 control chromosomes in the GnomAD database, including 49,843 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 0.81 (49843 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1733-38794G>A		intron_variant	Intron 12 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1733-38794G>A		intron_variant	Intron 12 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122660 AN: 151854 Hom.: 49818 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.808 AC: 122732 AN: 151972 Hom.: 49843 Cov.: 32 AF XY: 0.802 AC XY: 59631 AN XY: 74308

African (AFR) AF: 0.763 AC: 31648 AN: 41464

American (AMR) AF: 0.783 AC: 11963 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2939 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3967 AN: 5156

South Asian (SAS) AF: 0.830 AC: 4007 AN: 4826

European-Finnish (FIN) AF: 0.749 AC: 7899 AN: 10546

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.848 AC: 57583 AN: 67918

Other (OTH) AF: 0.794 AC: 1675 AN: 2110

Alfa AF: 0.827 Hom.: 21402

Bravo AF: 0.809

Asia WGS AF: 0.815 AC: 2835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.56
PhyloP100		-0.36
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: rs7088181; hg19: chr10-68079173;