8-143925134-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_201384.3(PLEC):c.4795G>A(p.Glu1599Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 1,558,926 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. E1599Q) 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 -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.4795G>A | p.Glu1599Lys | missense_variant | Exon 31 of 32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.4753G>A | p.Glu1585Lys | missense_variant | Exon 31 of 32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152048Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000130 AC: 21AN: 161680Hom.: 0 AF XY: 0.0000447 AC XY: 4AN XY: 89580
GnomAD4 exome AF: 0.0000540 AC: 76AN: 1406878Hom.: 0 Cov.: 69 AF XY: 0.0000517 AC XY: 36AN XY: 696900
GnomAD4 genome AF: 0.000375 AC: 57AN: 152048Hom.: 0 Cov.: 35 AF XY: 0.000390 AC XY: 29AN XY: 74266
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Inborn genetic diseases Uncertain:1
The c.4876G>A (p.E1626K) alteration is located in exon 32 (coding exon 31) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 4876, causing the glutamic acid (E) at amino acid position 1626 to be replaced by a lysine (K). 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1626 of the PLEC protein (p.Glu1626Lys). This variant is present in population databases (rs782412083, gnomAD 0.1%). 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: 573120). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at