rs782756562
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000345136.8(PLEC):c.10950G>T(p.Glu3650Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E3650E) has been classified as Likely benign.
Frequency
Consequence
ENST00000345136.8 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.10950G>T | p.Glu3650Asp | missense_variant | 32/32 | ENST00000345136.8 | NP_958786.1 | |
PLEC | NM_201378.4 | c.10908G>T | p.Glu3636Asp | missense_variant | 32/32 | ENST00000356346.7 | NP_958780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.10950G>T | p.Glu3650Asp | missense_variant | 32/32 | 1 | NM_201384.3 | ENSP00000344848 | ||
PLEC | ENST00000356346.7 | c.10908G>T | p.Glu3636Asp | missense_variant | 32/32 | 1 | NM_201378.4 | ENSP00000348702 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247606Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134862
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460542Hom.: 0 Cov.: 70 AF XY: 0.00000275 AC XY: 2AN XY: 726652
GnomAD4 genome Cov.: 33
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 | Sep 04, 2018 | This sequence change replaces glutamic acid with aspartic acid at codon 3677 of the PLEC protein (p.Glu3677Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs782756562, ExAC 0.002%). This variant has not been reported in the literature in individuals with PLEC-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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