rs376665854
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_201384.3(PLEC):c.3070G>A(p.Ala1024Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,567,488 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.3070G>A | p.Ala1024Thr | missense_variant | 24/32 | ENST00000345136.8 | NP_958786.1 | |
PLEC | NM_201378.4 | c.3028G>A | p.Ala1010Thr | missense_variant | 24/32 | ENST00000356346.7 | NP_958780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.3070G>A | p.Ala1024Thr | missense_variant | 24/32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.3028G>A | p.Ala1010Thr | missense_variant | 24/32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.000972 AC: 148AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000172 AC: 30AN: 174870Hom.: 0 AF XY: 0.000157 AC XY: 15AN XY: 95458
GnomAD4 exome AF: 0.0000954 AC: 135AN: 1415182Hom.: 0 Cov.: 41 AF XY: 0.0000985 AC XY: 69AN XY: 700270
GnomAD4 genome AF: 0.000972 AC: 148AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000940 AC XY: 70AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 03, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 10, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 13, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2023 | 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 14, 2024 | - - |
PLEC-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 07, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at