rs782667629
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_002230.4(JUP):c.804C>T(p.Asp268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,886 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
JUP
NM_002230.4 synonymous
NM_002230.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.44
Genes affected
JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-41767484-G-A is Benign according to our data. Variant chr17-41767484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 221029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.44 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.804C>T | p.Asp268= | synonymous_variant | 5/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.804C>T | p.Asp268= | synonymous_variant | 5/14 | 1 | NM_002230.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251400Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135876
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461830Hom.: 0 Cov.: 46 AF XY: 0.0000358 AC XY: 26AN XY: 727216
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74286
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2020 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at