rs7915695

Variant names:

• chr10-66684976-T-C
• rs7915695
• NM_013266.4:c.1282-63192A>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.1282-63192A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,242 control chromosomes in the GnomAD database, including 1,952 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 0.14 (1952 hom., cov: 29)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1282-63192A>G		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.1282-63192A>G		intron	N/A	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1282-63192A>G		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1282-63192A>G		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1282-63192A>G		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21289 AN: 151132 Hom.: 1952 Cov.: 29

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.141 AC: 21310 AN: 151242 Hom.: 1952 Cov.: 29 AF XY: 0.137 AC XY: 10124 AN XY: 73896

African (AFR) AF: 0.247 AC: 10182 AN: 41222

American (AMR) AF: 0.101 AC: 1529 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3464

East Asian (EAS) AF: 0.115 AC: 589 AN: 5140

South Asian (SAS) AF: 0.135 AC: 650 AN: 4806

European-Finnish (FIN) AF: 0.0676 AC: 699 AN: 10344

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.0997 AC: 6757 AN: 67788

Other (OTH) AF: 0.144 AC: 301 AN: 2096

Alfa AF: 0.109 Hom.: 1409

Bravo AF: 0.147

Asia WGS AF: 0.135 AC: 464 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		0.028
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: rs7915695; hg19: chr10-68444734;