rs61749223

Positions:

chr10-67521943-A-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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 -18 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CTNA3_HUMAN

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 ClinVar as [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 Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3000 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4 linkuse as main transcript	c.478T>A	p.Ser160Thr	missense_variant	5/18	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7 linkuse as main transcript	c.478T>A	p.Ser160Thr	missense_variant	5/18	1	NM_013266.4	ENSP00000389714	P1	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

GnomAD3 exomes

AF:

0.0232

AC:

5832

AN:

250916

Hom.:

AF XY:

0.0249

AC XY:

3375

AN XY:

135624

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 SAS exome

AF:

0.0399

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

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0318

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0412

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0252

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0197

AC:

3000

AN:

152256

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1537

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0371

Gnomad4 FIN

AF:

0.0303

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0218

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

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 13, 2019	This variant is associated with the following publications: (PMID: 29767709) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

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;.

MutationTaster

Benign

0.80

N;N;N

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

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