8-143918890-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS1_Supporting
The NM_201384.3(PLEC):c.10931G>A(p.Arg3644His) variant causes a missense change. The variant allele was found at a frequency of 0.0000602 in 1,611,952 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3644C) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.10931G>A | p.Arg3644His | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.10889G>A | p.Arg3630His | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.10931G>A | p.Arg3644His | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.10889G>A | p.Arg3630His | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000527 AC: 13AN: 246688Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134486
GnomAD4 exome AF: 0.0000541 AC: 79AN: 1459728Hom.: 0 Cov.: 69 AF XY: 0.0000523 AC XY: 38AN XY: 726298
GnomAD4 genome AF: 0.000118 AC: 18AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74358
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.11012G>A (p.R3671H) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 11012, causing the arginine (R) at amino acid position 3671 to be replaced by a histidine (H). 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 | Oct 03, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3671 of the PLEC protein (p.Arg3671His). This variant is present in population databases (rs368249132, gnomAD 0.03%). 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: 581642). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | Dec 17, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at