rs7077638

Variant names:

• chr10-66567257-A-G
• rs7077638
• NM_013266.4:c.1375-46484T>C

Variant summary

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

The NM_013266.4(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 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 4 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

ENSG00000298814 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1375-46484T>C		intron_variant	Intron 10 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1375-46484T>C		intron_variant	Intron 10 of 17	1	NM_013266.4	ENSP00000389714.1

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

African (AFR) AF: 0.547 AC: 22601 AN: 41334

American (AMR) AF: 0.450 AC: 6868 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2198 AN: 3462

East Asian (EAS) AF: 0.646 AC: 3323 AN: 5144

South Asian (SAS) AF: 0.731 AC: 3506 AN: 4794

European-Finnish (FIN) AF: 0.490 AC: 5152 AN: 10504

Middle Eastern (MID) AF: 0.666 AC: 193 AN: 290

European-Non Finnish (NFE) AF: 0.511 AC: 34686 AN: 67814

Other (OTH) AF: 0.545 AC: 1147 AN: 2106

Alfa AF: 0.528 Hom.: 11114

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
PhyloP100		-0.48
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: rs7077638; hg19: chr10-68327015;