rs372145644
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1
The NM_002230.4(JUP):c.633C>T(p.Asn211Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.000062 in 1,613,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002230.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.633C>T | p.Asn211Asn | synonymous_variant | Exon 4 of 14 | ENST00000393931.8 | NP_002221.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000770 AC: 19AN: 246866Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133846
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1460756Hom.: 1 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 726634
GnomAD4 genome AF: 0.000341 AC: 52AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
This is a synonymous variant occurring in gnomAD with a total MAF of 0.0070% and highest MAF of 0.1002%. This position is not strongly conserved and this variant is not predicted to impact splicing as it is located 75bp from the nearest splice site. This variant is not present in the literature in association with disease. Considering the evidence, this variant is Likely Benign. -
p.Asn211Asn in exon 4 of JUP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 0.1% (2/3738) of Africa n American chromosomes from a broad population by the NHLBI Exome Sequencing Pro ject (http://evs.gs.washington.edu/EVS; dbSNP rs372145644). -
JUP-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Cardiovascular phenotype Benign:1
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. -
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at