rs397517299
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002230.4(JUP):c.1849G>A(p.Ala617Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A617V) has been classified as Likely benign.
Frequency
Consequence
NM_002230.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.1849G>A | p.Ala617Thr | missense_variant | 11/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.1849G>A | p.Ala617Thr | missense_variant | 11/14 | 1 | NM_002230.4 | P1 | |
JUP | ENST00000310706.9 | c.1849G>A | p.Ala617Thr | missense_variant | 11/15 | 1 | P1 | ||
JUP | ENST00000393930.5 | c.1849G>A | p.Ala617Thr | missense_variant | 11/15 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 38
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 617 of the JUP protein (p.Ala617Thr). This variant has not been reported in the literature in individuals affected with JUP-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 45841). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 03, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 30, 2013 | The Ala617Thr variant in JUP has not been previously reported in the literature or identified by our laboratory. The frequency of this variant in large European American and African American populations cannot be determined from the NHLBI E xome Sequencing Project (http://evs.gs.washington.edu/EVS/), because coverage at this position was insufficient or unavailable. Computational analyses (biochemi cal amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the variant may not impact the protein, though this information is not pre dictive enough to rule out pathogenicity. In summary, additional information is needed to fully assess the clinical significance of the Ala617Thr variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at