rs7077638

Positions:

• chr10-66567257-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000433211.7(CTNNA3):​c.1375-46484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,598 control chromosomes in the GnomAD database, including 21,522 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 0.53 (21522 hom., cov: 30)
• Consequence: CTNNA3 ENST00000433211.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1375-46484T>C		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1375-46484T>C		intron_variant		1	NM_013266.4	ENSP00000389714	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80152 AN: 151480 Hom.: 21488 Cov.: 30

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.529 AC: 80240 AN: 151598 Hom.: 21522 Cov.: 30 AF XY: 0.533 AC XY: 39501 AN XY: 74114

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.545

Alfa AF: 0.529 Hom.: 9991

Bravo AF: 0.520

Asia WGS AF: 0.693 AC: 2412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.67
DANN	Benign	0.74

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: rs7077638; hg19: chr10-68327015;