rs61735044

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_013266.4(CTNNA3):c.33C>T(p.Ile11Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,200 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I11I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 6 hom. )

Consequence

CTNNA3
NM_013266.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.600

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-67647481-G-A is Benign according to our data. Variant chr10-67647481-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 240870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.6 with no splicing effect.

BS2

High AC in GnomAd4 at 297 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4 link	c.33C>T	p.Ile11Ile	synonymous_variant	Exon 2 of 18	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7 link	c.33C>T	p.Ile11Ile	synonymous_variant	Exon 2 of 18	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00167

AC:

418

AN:

250874

AF XY:

0.00157

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000899

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00289

AC:

4218

AN:

1461014

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2042

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33448

American (AMR)

AF:

0.00103

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00291

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.000750

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00345

AC:

3838

AN:

1111398

Other (OTH)

AF:

0.00306

AC:

185

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

199

398

598

797

996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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:

0.00195

AC:

297

AN:

152186

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41532

American (AMR)

AF:

0.00190

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00328

AC:

223

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00179

Hom.:

Bravo

AF:

0.00209

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00360

EpiControl

AF:

0.00208

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 11, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Oct 29, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:4

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 05, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CTNNA3: BP4, BP7 -

Arrhythmogenic right ventricular dysplasia 13

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.75

CADD

Benign

0.88

(source)

DANN

Benign

0.77

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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