rs61749223

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013266.4(CTNNA3):c.478T>A(p.Ser160Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0245 in 1,612,254 control chromosomes in the GnomAD database, including 600 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. S160S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.020 ( 38 hom., cov: 32)

Exomes 𝑓: 0.025 ( 562 hom. )

Consequence

CTNNA3
NM_013266.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.09

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069077313).

BP6

Variant 10-67521943-A-T is Benign according to our data. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521943-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0197 (3000/152256) while in subpopulation SAS AF = 0.0371 (179/4828). AF 95% confidence interval is 0.0326. There are 38 homozygotes in GnomAd4. There are 1537 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3000 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4 link	c.478T>A	p.Ser160Thr	missense_variant	Exon 5 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.478T>A	p.Ser160Thr	missense_variant	Exon 5 of 18	1	NM_013266.4	ENSP00000389714.1		Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

3003

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0232

AC:

5832

AN:

250916

AF XY:

0.0249

show subpopulations

Gnomad AFR exome

AF:

0.00320

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.0249

Gnomad OTH exome

AF:

0.0243

GnomAD4 exome

AF:

0.0250

AC:

36428

AN:

1459998

Hom.:

562

Cov.:

AF XY:

0.0256

AC XY:

18578

AN XY:

726344

show subpopulations

African (AFR)

AF:

0.00299

AC:

100

AN:

33434

American (AMR)

AF:

0.0175

AC:

780

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

829

AN:

26082

East Asian (EAS)

AF:

0.000176

AC:

AN:

39686

South Asian (SAS)

AF:

0.0412

AC:

3546

AN:

86032

European-Finnish (FIN)

AF:

0.0296

AC:

1579

AN:

53370

Middle Eastern (MID)

AF:

0.0301

AC:

173

AN:

5756

European-Non Finnish (NFE)

AF:

0.0252

AC:

27947

AN:

1110774

Other (OTH)

AF:

0.0243

AC:

1467

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1584

3169

4753

6338

7922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1070

2140

3210

4280

5350

<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:

0.0197

AC:

3000

AN:

152256

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1537

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00419

AC:

174

AN:

41552

American (AMR)

AF:

0.0250

AC:

382

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0371

AC:

179

AN:

4828

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0262

AC:

1782

AN:

68014

Other (OTH)

AF:

0.0218

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0242

Hom.:

Bravo

AF:

0.0171

TwinsUK

AF:

0.0248

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0253

AC:

218

ExAC

AF:

0.0226

AC:

2740

Asia WGS

AF:

0.0130

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:5

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 09, 2023

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

Significance:Likely 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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29767709) -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.071

T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.

PhyloP100

4.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.13

Sift

Benign

0.073

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.96

D;.

Vest4

0.15

MPC

0.034

ClinPred

0.029

GERP RS

5.2

Varity_R

0.11

gMVP

0.075

Mutation Taster

=97/3

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

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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