rs548876454
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_201384.3(PLEC):c.10445G>A(p.Arg3482His) variant causes a missense change. The variant allele was found at a frequency of 0.000062 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R3482C) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.10445G>A | p.Arg3482His | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.10403G>A | p.Arg3468His | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.10445G>A | p.Arg3482His | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.10403G>A | p.Arg3468His | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152234Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000683 AC: 17AN: 248966Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135178
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461378Hom.: 0 Cov.: 75 AF XY: 0.0000688 AC XY: 50AN XY: 727044
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152352Hom.: 0 Cov.: 34 AF XY: 0.0000268 AC XY: 2AN XY: 74500
ClinVar
Submissions by phenotype
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 27, 2023 | ClinVar contains an entry for this variant (Variation ID: 478526). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs548876454, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3509 of the PLEC protein (p.Arg3509His). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLEC protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at