10-66280531-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013266.4(CTNNA3):​c.1823A>C​(p.Asp608Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CTNNA3
NM_013266.4 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.83
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTNNA3NM_013266.4 linkc.1823A>C p.Asp608Ala missense_variant Exon 13 of 18 ENST00000433211.7 NP_037398.2 Q9UI47-1A8K141

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTNNA3ENST00000433211.7 linkc.1823A>C p.Asp608Ala missense_variant Exon 13 of 18 1 NM_013266.4 ENSP00000389714.1 Q9UI47-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457856
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725352
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-0.39
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-5.6
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.89
MutPred
0.64
Gain of loop (P = 0.069);
MVP
0.71
MPC
0.023
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.62
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-68040289; API