rs557562267
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_201384.3(PLEC):c.11020C>T(p.Arg3674Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R3674H) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.11020C>T | p.Arg3674Cys | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.10978C>T | p.Arg3660Cys | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.11020C>T | p.Arg3674Cys | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.10978C>T | p.Arg3660Cys | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000109 AC: 27AN: 247462Hom.: 0 AF XY: 0.0000963 AC XY: 13AN XY: 134954
GnomAD4 exome AF: 0.000118 AC: 173AN: 1460846Hom.: 0 Cov.: 68 AF XY: 0.000113 AC XY: 82AN XY: 726758
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 03, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 22, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2022 | The c.11101C>T (p.R3701C) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 11101, causing the arginine (R) at amino acid position 3701 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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 | Nov 19, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 3701 of the PLEC protein (p.Arg3701Cys). This variant is present in population databases (rs557562267, gnomAD 0.02%). 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: 586325). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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