Variant rs10997034 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013266.4(CTNNA3):c.1872C>A(p.Val624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,603,824 control chromosomes in the GnomAD database, including 1,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 305 hom., cov: 32)

Exomes 𝑓: 0.024 ( 927 hom. )

Consequence

CTNNA3
NM_013266.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.29

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-66280482-G-T is Benign according to our data. Variant chr10-66280482-G-T is described in ClinVar as [Benign]. Clinvar id is 415368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-66280482-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4 linkuse as main transcript	c.1872C>A	p.Val624=	synonymous_variant	13/18	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.1872C>A	p.Val624=	synonymous_variant	13/18	1	NM_013266.4	ENSP00000389714	P1	Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7142

AN:

151926

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.0574

Gnomad SAS

AF:

0.0893

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0398

GnomAD3 exomes

AF:

0.0342

AC:

8270

AN:

241960

Hom.:

312

AF XY:

0.0355

AC XY:

4650

AN XY:

131068

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.0489

Gnomad SAS exome

AF:

0.0841

Gnomad FIN exome

AF:

0.00652

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0268

GnomAD4 exome

AF:

0.0240

AC:

34798

AN:

1451780

Hom.:

927

Cov.:

AF XY:

0.0256

AC XY:

18516

AN XY:

722244

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.0553

Gnomad4 SAS exome

AF:

0.0814

Gnomad4 FIN exome

AF:

0.00700

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0471

AC:

7162

AN:

152044

Hom.:

305

Cov.:

AF XY:

0.0467

AC XY:

3468

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.0666

Gnomad4 EAS

AF:

0.0577

Gnomad4 SAS

AF:

0.0892

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0404

Alfa

AF:

0.0269

Hom.:

131

Bravo

AF:

0.0488

Asia WGS

AF:

0.0960

AC:

333

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Arrhythmogenic right ventricular dysplasia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.4

DANN

Benign

0.75

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