rs12942034
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002230.4(JUP):c.909+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,611,860 control chromosomes in the GnomAD database, including 522,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.81 ( 50207 hom., cov: 32)
Exomes 𝑓: 0.80 ( 472130 hom. )
Consequence
JUP
NM_002230.4 intron
NM_002230.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00800
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
?
Variant 17-41767362-A-G is Benign according to our data. Variant chr17-41767362-A-G is described in ClinVar as [Benign]. Clinvar id is 258593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41767362-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.909+17T>C | intron_variant | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.909+17T>C | intron_variant | 1 | NM_002230.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.808 AC: 122885AN: 152080Hom.: 50160 Cov.: 32
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GnomAD3 exomes AF: 0.751 AC: 188199AN: 250442Hom.: 72781 AF XY: 0.763 AC XY: 103377AN XY: 135472
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GnomAD4 exome AF: 0.801 AC: 1169037AN: 1459662Hom.: 472130 Cov.: 36 AF XY: 0.802 AC XY: 582409AN XY: 726206
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GnomAD4 genome ? AF: 0.808 AC: 122992AN: 152198Hom.: 50207 Cov.: 32 AF XY: 0.801 AC XY: 59600AN XY: 74392
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:7
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Naxos disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Cardiomyopathy Benign:1
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Arrhythmogenic right ventricular dysplasia 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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