rs200686790
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_201384.3(PLEC):c.2462C>T(p.Thr821Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,602,394 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 (★★).
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.2462C>T | p.Thr821Ile | missense_variant | Exon 21 of 32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.2420C>T | p.Thr807Ile | missense_variant | Exon 21 of 32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152214Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000123 AC: 28AN: 227802Hom.: 0 AF XY: 0.000112 AC XY: 14AN XY: 125504
GnomAD4 exome AF: 0.000128 AC: 185AN: 1450180Hom.: 0 Cov.: 65 AF XY: 0.000126 AC XY: 91AN XY: 721462
GnomAD4 genome AF: 0.000125 AC: 19AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10AN XY: 74362
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2543C>T (p.T848I) alteration is located in exon 22 (coding exon 21) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 2543, causing the threonine (T) at amino acid position 848 to be replaced by an isoleucine (I). 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 threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 848 of the PLEC protein (p.Thr848Ile). This variant is present in population databases (rs200686790, 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: 471553). 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at