rs375617818
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_201384.3(PLEC):c.3287G>A(p.Arg1096His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,601,370 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1096C) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.3287G>A | p.Arg1096His | missense_variant | 26/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.3245G>A | p.Arg1082His | missense_variant | 26/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.3287G>A | p.Arg1096His | missense_variant | 26/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.3245G>A | p.Arg1082His | missense_variant | 26/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152262Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000261 AC: 62AN: 237572Hom.: 1 AF XY: 0.000268 AC XY: 35AN XY: 130726
GnomAD4 exome AF: 0.000119 AC: 172AN: 1449108Hom.: 2 Cov.: 34 AF XY: 0.000122 AC XY: 88AN XY: 718568
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152262Hom.: 0 Cov.: 35 AF XY: 0.0000807 AC XY: 6AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 05, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at