Variant rs61749224 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_013266.4(CTNNA3):c.348A>C(p.Pro116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,613,772 control chromosomes in the GnomAD database, including 408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 23 hom., cov: 32)

Exomes 𝑓: 0.020 ( 385 hom. )

Consequence

CTNNA3
NM_013266.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.40

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-67539614-T-G is Benign according to our data. Variant chr10-67539614-T-G is described in ClinVar as [Benign]. Clinvar id is 220770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67539614-T-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0157 (2388/152254) while in subpopulation SAS AF= 0.0353 (170/4814). AF 95% confidence interval is 0.031. There are 23 homozygotes in gnomad4. There are 1094 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2388 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4 linkuse as main transcript	c.348A>C	p.Pro116=	synonymous_variant	4/18	ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7 linkuse as main transcript	c.348A>C	p.Pro116=	synonymous_variant	4/18	1	NM_013266.4	P1	Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2390

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0355

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0171

AC:

4281

AN:

250900

Hom.:

AF XY:

0.0185

AC XY:

2510

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0361

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0197

AC:

28775

AN:

1461518

Hom.:

385

Cov.:

AF XY:

0.0204

AC XY:

14816

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00954

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.00337

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0157

AC:

2388

AN:

152254

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1094

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0353

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.0205

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0218

EpiControl

AF:

0.0222

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Arrhythmogenic right ventricular dysplasia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.4

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over