Variant rs74142830 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000433211.7(CTNNA3):c.483C>T(p.Leu161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 1,613,020 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

CTNNA3
ENST00000433211.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.118

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 10-67521938-G-A is Benign according to our data. Variant chr10-67521938-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521938-G-A is described in Lovd as [Benign]. Variant chr10-67521938-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.118 with no splicing effect.

BS2

High AC in GnomAd4 at 358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4 linkuse as main transcript	c.483C>T	p.Leu161=	synonymous_variant	5/18	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7 linkuse as main transcript	c.483C>T	p.Leu161=	synonymous_variant	5/18	1	NM_013266.4	ENSP00000389714	P1	Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000557

AC:

140

AN:

251154

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000257

AC:

376

AN:

1460730

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

152

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00941

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00235

AC:

358

AN:

152290

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00820

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00243

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 17, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 20, 2022	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Arrhythmogenic right ventricular dysplasia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

CTNNA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.9

DANN

Benign

0.70

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

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