rs146475470

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013266.4(CTNNA3):c.880G>A(p.Glu294Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E294E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CTNNA3
NM_013266.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.17

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058566093).

BS2

High AC in GnomAd4 at 43 Unknown,AD 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	UniProt
CTNNA3	NM_013266.4	MANE Select	c.880G>A	p.Glu294Lys	missense	Exon 7 of 18	NP_037398.2	Q9UI47-1
CTNNA3	NM_001127384.3		c.880G>A	p.Glu294Lys	missense	Exon 7 of 18	NP_001120856.1	Q9UI47-1
CTNNA3	NM_001291133.2		c.916G>A	p.Glu306Lys	missense	Exon 8 of 9	NP_001278062.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.880G>A	p.Glu294Lys	missense	Exon 7 of 18	ENSP00000389714.1	Q9UI47-1
CTNNA3	ENST00000682758.1		c.880G>A	p.Glu294Lys	missense	Exon 8 of 19	ENSP00000508047.1	Q9UI47-1
CTNNA3	ENST00000684154.1		c.880G>A	p.Glu294Lys	missense	Exon 7 of 18	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251052

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33452

American (AMR)

AF:

0.0000895

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111804

Other (OTH)

AF:

0.000116

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000282

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41548

American (AMR)

AF:

0.000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000296

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arrhythmogenic right ventricular dysplasia 13 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.059

Eigen

Benign

-0.21

Eigen_PC

Benign

0.018

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0083

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

6.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.40

REVEL

Benign

0.067

Sift

Benign

0.69

Sift4G

Benign

0.80

Polyphen

0.0060

Vest4

0.45

MVP

0.47

MPC

0.091

ClinPred

0.067

GERP RS

4.9

PromoterAI

-0.0067

Neutral

(source)

Varity_R

0.077

gMVP

0.34

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over