chr17-41769551-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_002230.4(JUP):āc.335A>Gā(p.Asn112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,608,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002230.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.335A>G | p.Asn112Ser | missense_variant | 3/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.335A>G | p.Asn112Ser | missense_variant | 3/14 | 1 | NM_002230.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 15AN: 235812Hom.: 0 AF XY: 0.0000936 AC XY: 12AN XY: 128198
GnomAD4 exome AF: 0.0000275 AC: 40AN: 1456306Hom.: 0 Cov.: 34 AF XY: 0.0000345 AC XY: 25AN XY: 724148
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces asparagine with serine at codon 112 of the JUP protein (p.Asn112Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs372364561, ExAC 0.06%). This variant has not been reported in the literature in individuals affected with JUP-related conditions. ClinVar contains an entry for this variant (Variation ID: 191677). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at