rs2133696

Variant names:

• chr10-67539960-A-G
• rs2133696
• NM_013266.4:c.293-291T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013266.4(CTNNA3):​c.293-291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,098 control chromosomes in the GnomAD database, including 4,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (4961 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527
• 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-67539960-A-G is Benign according to our data. Variant chr10-67539960-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.293-291T>C		intron_variant	Intron 3 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.293-291T>C		intron_variant	Intron 3 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30030 AN: 151980 Hom.: 4926 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.198 AC: 30118 AN: 152098 Hom.: 4961 Cov.: 32 AF XY: 0.194 AC XY: 14398 AN XY: 74352

African (AFR) AF: 0.458 AC: 18979 AN: 41458

American (AMR) AF: 0.114 AC: 1742 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3468

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5182

South Asian (SAS) AF: 0.167 AC: 806 AN: 4826

European-Finnish (FIN) AF: 0.0896 AC: 949 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6930 AN: 67978

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.132 Hom.: 1162

Bravo AF: 0.208

Asia WGS AF: 0.121 AC: 422 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.71
PhyloP100		0.53
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: rs2133696; hg19: chr10-69299718;