rs74142830
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_013266.4(CTNNA3):c.483C>T(p.Leu161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 1,613,020 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 1 hom. )
Consequence
CTNNA3
NM_013266.4 synonymous
NM_013266.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.118
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 10-67521938-G-A is Benign according to our data. Variant chr10-67521938-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-67521938-G-A is described in Lovd as [Benign]. Variant chr10-67521938-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.118 with no splicing effect.
BS2
?
High AC in GnomAd4 at 358 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNA3 | NM_013266.4 | c.483C>T | p.Leu161= | synonymous_variant | 5/18 | ENST00000433211.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNA3 | ENST00000433211.7 | c.483C>T | p.Leu161= | synonymous_variant | 5/18 | 1 | NM_013266.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00235 AC: 357AN: 152172Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
357
AN:
152172
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: 0.000557 AC: 140AN: 251154Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135744
GnomAD3 exomes
AF:
AC:
140
AN:
251154
Hom.:
AF XY:
AC XY:
47
AN XY:
135744
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: 0.000257 AC: 376AN: 1460730Hom.: 1 Cov.: 31 AF XY: 0.000209 AC XY: 152AN XY: 726690
GnomAD4 exome
AF:
AC:
376
AN:
1460730
Hom.:
Cov.:
31
AF XY:
AC XY:
152
AN XY:
726690
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: 0.00235 AC: 358AN: 152290Hom.: 1 Cov.: 32 AF XY: 0.00218 AC XY: 162AN XY: 74456
GnomAD4 genome
?
AF:
AC:
358
AN:
152290
Hom.:
Cov.:
32
AF XY:
AC XY:
162
AN XY:
74456
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:
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 17, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:2
Likely 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 | GeneDx | Jul 14, 2020 | - - |
Arrhythmogenic right ventricular dysplasia 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
CTNNA3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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