10-67539614-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_013266.4(CTNNA3):c.348A>C(p.Pro116Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,613,772 control chromosomes in the GnomAD database, including 408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 23 hom., cov: 32)

Exomes 𝑓: 0.020 ( 385 hom. )

Consequence

CTNNA3
NM_013266.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -5.40

Publications

7 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 -16 ACMG points.

BP6

Variant 10-67539614-T-G is Benign according to our data. Variant chr10-67539614-T-G is described in ClinVar as Benign. ClinVar VariationId is 220770.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 = 0.0157 (2388/152254) while in subpopulation SAS AF = 0.0353 (170/4814). AF 95% confidence interval is 0.031. There are 23 homozygotes in GnomAd4. There are 1094 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2388 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CTNNA3	NM_013266.4	MANE Select	c.348A>C	p.Pro116Pro	synonymous	Exon 4 of 18	NP_037398.2
CTNNA3	NM_001127384.3		c.348A>C	p.Pro116Pro	synonymous	Exon 4 of 18	NP_001120856.1
CTNNA3	NM_001291133.2		c.384A>C	p.Pro128Pro	synonymous	Exon 5 of 9	NP_001278062.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.348A>C	p.Pro116Pro	synonymous	Exon 4 of 18	ENSP00000389714.1
CTNNA3	ENST00000682758.1		c.348A>C	p.Pro116Pro	synonymous	Exon 5 of 19	ENSP00000508047.1
CTNNA3	ENST00000684154.1		c.348A>C	p.Pro116Pro	synonymous	Exon 4 of 18	ENSP00000508371.1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2390

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0355

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.0171

AC:

4281

AN:

250900

AF XY:

0.0185

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0197

AC:

28775

AN:

1461518

Hom.:

385

Cov.:

AF XY:

0.0204

AC XY:

14816

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.00954

AC:

319

AN:

33450

American (AMR)

AF:

0.0128

AC:

574

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

352

AN:

26124

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.0349

AC:

3011

AN:

86252

European-Finnish (FIN)

AF:

0.00337

AC:

180

AN:

53412

Middle Eastern (MID)

AF:

0.0401

AC:

231

AN:

5764

European-Non Finnish (NFE)

AF:

0.0206

AC:

22906

AN:

1111754

Other (OTH)

AF:

0.0198

AC:

1198

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1397

2795

4192

5590

6987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.0157

AC:

2388

AN:

152254

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1094

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00994

AC:

413

AN:

41562

American (AMR)

AF:

0.0167

AC:

255

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0353

AC:

170

AN:

4814

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0205

AC:

1393

AN:

68014

Other (OTH)

AF:

0.0156

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0189

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0218

EpiControl

AF:

0.0222

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 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

Sep 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.4

(source)

DANN

Benign

0.59

PhyloP100

-5.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over