chr8-143924012-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_201384.3(PLEC):āc.5917C>Gā(p.Arg1973Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,435,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1973Q) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.5917C>G | p.Arg1973Gly | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.5875C>G | p.Arg1959Gly | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.5917C>G | p.Arg1973Gly | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.5875C>G | p.Arg1959Gly | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes Cov.: 36
GnomAD4 exome AF: 0.00000209 AC: 3AN: 1435988Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0AN XY: 714096
GnomAD4 genome Cov.: 36
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 03, 2022 | This variant disrupts the p.Arg2000 amino acid residue in PLEC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11851880, 22854623, 29453417). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C45"). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2000 of the PLEC protein (p.Arg2000Gly). 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