rs782716612
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_201384.3(PLEC):c.2540G>A(p.Ser847Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,432,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. S847S) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.2540G>A | p.Ser847Asn | missense_variant | 21/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.2498G>A | p.Ser833Asn | missense_variant | 21/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.2540G>A | p.Ser847Asn | missense_variant | 21/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.2498G>A | p.Ser833Asn | missense_variant | 21/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000800 AC: 16AN: 199926Hom.: 0 AF XY: 0.0000633 AC XY: 7AN XY: 110534
GnomAD4 exome AF: 0.0000133 AC: 19AN: 1432306Hom.: 0 Cov.: 65 AF XY: 0.0000141 AC XY: 10AN XY: 711424
GnomAD4 genome ? Cov.: 34
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 | Jul 31, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 538927). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs782716612, gnomAD 0.05%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 874 of the PLEC protein (p.Ser874Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at