rs201884310
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_201384.3(PLEC):c.1387C>T(p.Arg463Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,612,884 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. R463Q) 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.1387C>T | p.Arg463Trp | missense_variant | 13/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.1345C>T | p.Arg449Trp | missense_variant | 13/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.1387C>T | p.Arg463Trp | missense_variant | 13/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.1345C>T | p.Arg449Trp | missense_variant | 13/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000646 AC: 16AN: 247578Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 134954
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1460614Hom.: 0 Cov.: 60 AF XY: 0.0000261 AC XY: 19AN XY: 726628
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74456
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The c.1468C>T (p.R490W) alteration is located in exon 14 (coding exon 13) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 1468, causing the arginine (R) at amino acid position 490 to be replaced by a tryptophan (W). 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 | Dec 15, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 490 of the PLEC protein (p.Arg490Trp). This variant is present in population databases (rs201884310, 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: 583097). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 11, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at