CTNNA3 p.Arg378Cys

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_013266.4(CTNNA3):c.1132C>T(p.Arg378Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000607 in 1,602,088 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

CTNNA3
NM_013266.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 3.99

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

new If you want to explore the variant's impact on the transcript NM_013266.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 10-66766413-G-A is Benign according to our data. Variant chr10-66766413-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 409017.

BS2

High AC in GnomAd4 at 67 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1132C>T	p.Arg378Cys	missense	Exon 9 of 18	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.1132C>T	p.Arg378Cys	missense	Exon 9 of 18	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1132C>T	p.Arg378Cys	missense	Exon 9 of 18	ENSP00000389714.1	Q9UI47-1
CTNNA3	ENST00000682758.1		c.1132C>T	p.Arg378Cys	missense	Exon 10 of 19	ENSP00000508047.1	Q9UI47-1
CTNNA3	ENST00000684154.1		c.1132C>T	p.Arg378Cys	missense	Exon 9 of 18	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000756

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000469

AC:

114

AN:

242920

AF XY:

0.000504

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad FIN exome

AF:

0.000516

Gnomad NFE exome

AF:

0.000724

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000625

AC:

906

AN:

1449968

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

451

AN XY:

720494

show subpopulations

African (AFR)

AF:

0.0000606

AC:

AN:

33004

American (AMR)

AF:

0.000347

AC:

AN:

43182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25680

East Asian (EAS)

AF:

0.000126

AC:

AN:

39582

South Asian (SAS)

AF:

0.000215

AC:

AN:

83544

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.000732

AC:

810

AN:

1106396

Other (OTH)

AF:

0.000501

AC:

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000440

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41504

American (AMR)

AF:

0.000262

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.000756

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000525

Hom.:

Bravo

AF:

0.000332

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Arrhythmogenic right ventricular dysplasia 13 (1)

CTNNA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.1

PhyloP100

4.0

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.27

Sift

Benign

0.099

Sift4G

Benign

0.23

Varity_R

0.22

gMVP

0.42

Mutation Taster

=96/4

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over