rs781960031
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_201384.3(PLEC):c.11735G>A(p.Arg3912Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,596,468 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.11735G>A | p.Arg3912Gln | missense_variant | 32/32 | ENST00000345136.8 | NP_958786.1 | |
PLEC | NM_201378.4 | c.11693G>A | p.Arg3898Gln | 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.11735G>A | p.Arg3912Gln | missense_variant | 32/32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.11693G>A | p.Arg3898Gln | missense_variant | 32/32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000173 AC: 37AN: 214364Hom.: 0 AF XY: 0.000211 AC XY: 25AN XY: 118304
GnomAD4 exome AF: 0.000125 AC: 181AN: 1444274Hom.: 0 Cov.: 56 AF XY: 0.000157 AC XY: 113AN XY: 717902
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 18, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2019 | - - |
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 | Jan 21, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3939 of the PLEC protein (p.Arg3939Gln). This variant is present in population databases (rs781960031, gnomAD 0.07%). 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: 378373). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at