Variant rs192093851 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013266.4(CTNNA3):c.742G>T(p.Ala248Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00106 in 1,614,092 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 11 hom. )

Consequence

CTNNA3
NM_013266.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.40

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009857684).

BP6

Variant 10-67219708-C-A is Benign according to our data. Variant chr10-67219708-C-A is described in ClinVar as [Benign]. Clinvar id is 415370.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 271 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4 link	c.742G>T	p.Ala248Ser	missense_variant	6/18	ENST00000433211.7	NP_037398.2	Q9UI47-1A8K141

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7 link	c.742G>T	p.Ala248Ser	missense_variant	6/18	1	NM_013266.4	ENSP00000389714.1		Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

271

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00244

AC:

614

AN:

251392

Hom.:

AF XY:

0.00230

AC XY:

312

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0243

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000984

AC:

1439

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000932

AC XY:

678

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.000144

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152246

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00208

AC:

253

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0099

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.14

T;D

Polyphen

1.0

D;.

Vest4

0.49

MVP

0.56

MPC

0.099

ClinPred

0.086

GERP RS

5.5

Varity_R

0.61

gMVP

0.31

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