rs554022624
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000345136.8(PLEC):c.1759C>T(p.Arg587Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,607,658 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. R587Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000345136.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.1759C>T | p.Arg587Trp | missense_variant | 15/32 | ENST00000345136.8 | NP_958786.1 | |
PLEC | NM_201378.4 | c.1717C>T | p.Arg573Trp | missense_variant | 15/32 | ENST00000356346.7 | NP_958780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.1759C>T | p.Arg587Trp | missense_variant | 15/32 | 1 | NM_201384.3 | ENSP00000344848 | ||
PLEC | ENST00000356346.7 | c.1717C>T | p.Arg573Trp | missense_variant | 15/32 | 1 | NM_201378.4 | ENSP00000348702 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000567 AC: 13AN: 229428Hom.: 0 AF XY: 0.0000396 AC XY: 5AN XY: 126386
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1455492Hom.: 0 Cov.: 65 AF XY: 0.0000152 AC XY: 11AN XY: 723832
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74410
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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 567914). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs554022624, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 614 of the PLEC protein (p.Arg614Trp). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 24, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at