rs370266957
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_201384.3(PLEC):c.9394C>T(p.Arg3132Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000194 in 1,596,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R3132H) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.9394C>T | p.Arg3132Cys | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.9352C>T | p.Arg3118Cys | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.9394C>T | p.Arg3132Cys | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.9352C>T | p.Arg3118Cys | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000559 AC: 13AN: 232660Hom.: 0 AF XY: 0.0000468 AC XY: 6AN XY: 128144
GnomAD4 exome AF: 0.0000173 AC: 25AN: 1444644Hom.: 0 Cov.: 73 AF XY: 0.0000167 AC XY: 12AN XY: 717750
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152346Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 22, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 29, 2022 | - - |
Epidermolysis bullosa simplex, Ogna type;C2677349:Epidermolysis bullosa simplex 5C, with pyloric atresia;C2931072:Epidermolysis bullosa simplex 5B, with muscular dystrophy;C3150989:Autosomal recessive limb-girdle muscular dystrophy type 2Q;C4225309:Epidermolysis bullosa simplex with nail dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3159 of the PLEC protein (p.Arg3159Cys). This variant is present in population databases (rs370266957, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. ClinVar contains an entry for this variant (Variation ID: 448082). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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