rs7915695

Positions:

• chr10-66684976-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1282-63192A>G		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1282-63192A>G		intron_variant		1	NM_013266.4	ENSP00000389714	P1

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.144

Alfa AF: 0.107 Hom.: 1181

Bravo AF: 0.147

Asia WGS AF: 0.135 AC: 464 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs7915695; hg19: chr10-68444734;