rs781844059
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201384.3(PLEC):c.5474C>T(p.Ala1825Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,551,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.5474C>T | p.Ala1825Val | missense_variant | Exon 31 of 32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.5432C>T | p.Ala1811Val | missense_variant | Exon 31 of 32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.0000266 AC: 4AN: 150446Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000246 AC: 4AN: 162530Hom.: 0 AF XY: 0.0000109 AC XY: 1AN XY: 91608
GnomAD4 exome AF: 0.0000300 AC: 42AN: 1400696Hom.: 0 Cov.: 68 AF XY: 0.0000187 AC XY: 13AN XY: 694408
GnomAD4 genome AF: 0.0000266 AC: 4AN: 150446Hom.: 0 Cov.: 34 AF XY: 0.0000136 AC XY: 1AN XY: 73452
ClinVar
Submissions by phenotype
not provided Uncertain:2
- -
- -
Inborn genetic diseases Uncertain:1
The c.5555C>T (p.A1852V) alteration is located in exon 32 (coding exon 31) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 5555, causing the alanine (A) at amino acid position 1852 to be replaced by a valine (V). 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
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1852 of the PLEC protein (p.Ala1852Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 499642). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The valine 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