rs77165728
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_013266.4(CTNNA3):c.1900G>A(p.Glu634Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000651 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 0 hom. )
Consequence
CTNNA3
NM_013266.4 missense
NM_013266.4 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 3.62
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 Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21713498).
BP6
Variant 10-66103234-C-T is Benign according to our data. Variant chr10-66103234-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 240866.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2}. Variant chr10-66103234-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 84 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTNNA3 | NM_013266.4 | c.1900G>A | p.Glu634Lys | missense_variant | 14/18 | ENST00000433211.7 | NP_037398.2 | |
LOC105378340 | XR_007062172.1 | n.226+4417C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTNNA3 | ENST00000433211.7 | c.1900G>A | p.Glu634Lys | missense_variant | 14/18 | 1 | NM_013266.4 | ENSP00000389714 | P1 | |
ENST00000608793.1 | n.485+4417C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000552 AC: 84AN: 152160Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
84
AN:
152160
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000537 AC: 135AN: 251302Hom.: 0 AF XY: 0.000596 AC XY: 81AN XY: 135814
GnomAD3 exomes
AF:
AC:
135
AN:
251302
Hom.:
AF XY:
AC XY:
81
AN XY:
135814
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000661 AC: 966AN: 1461616Hom.: 0 Cov.: 30 AF XY: 0.000646 AC XY: 470AN XY: 727126
GnomAD4 exome
AF:
AC:
966
AN:
1461616
Hom.:
Cov.:
30
AF XY:
AC XY:
470
AN XY:
727126
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000552 AC: 84AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74454
GnomAD4 genome
AF:
AC:
84
AN:
152278
Hom.:
Cov.:
32
AF XY:
AC XY:
40
AN XY:
74454
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
5
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
6
ExAC
AF:
AC:
55
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 13 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Phosphorus, Inc. | Aug 01, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2022 | The p.E634K variant (also known as c.1900G>A), located in coding exon 13 of the CTNNA3 gene, results from a G to A substitution at nucleotide position 1900. The glutamic acid at codon 634 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 06, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at