rs10997034

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013266.4(CTNNA3):c.1872C>A(p.Val624Val) 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

Publications

6 publications found

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 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

CTNNA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 415368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4 link	c.1872C>A	p.Val624Val	synonymous_variant	Exon 13 of 18	ENST00000433211.7	NP_037398.2	Q9UI47-1A8K141

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7 link	c.1872C>A	p.Val624Val	synonymous_variant	Exon 13 of 18	1	NM_013266.4	ENSP00000389714.1		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

GnomAD2 exomes

AF:

0.0342

AC:

8270

AN:

241960

AF XY:

0.0355

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 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

African (AFR)

AF:

0.110

AC:

3569

AN:

32492

American (AMR)

AF:

0.0125

AC:

540

AN:

43256

Ashkenazi Jewish (ASJ)

AF:

0.0639

AC:

1657

AN:

25918

East Asian (EAS)

AF:

0.0553

AC:

2159

AN:

39022

South Asian (SAS)

AF:

0.0814

AC:

6893

AN:

84704

European-Finnish (FIN)

AF:

0.00700

AC:

368

AN:

52590

Middle Eastern (MID)

AF:

0.0644

AC:

369

AN:

5726

European-Non Finnish (NFE)

AF:

0.0154

AC:

17109

AN:

1108132

Other (OTH)

AF:

0.0356

AC:

2134

AN:

59940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

1555

3110

4664

6219

7774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0471

AC:

7162

AN:

152044

Hom.:

305

Cov.:

AF XY:

0.0467

AC XY:

3468

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.109

AC:

4525

AN:

41504

American (AMR)

AF:

0.0204

AC:

310

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

231

AN:

3466

East Asian (EAS)

AF:

0.0577

AC:

298

AN:

5164

South Asian (SAS)

AF:

0.0892

AC:

430

AN:

4820

European-Finnish (FIN)

AF:

0.00538

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0176

AC:

1194

AN:

67962

Other (OTH)

AF:

0.0404

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

344

688

1033

1377

1721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0289

Hom.:

178

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

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 26, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.4

(source)

DANN

Benign

0.75

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over