rs370569372
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_201384.3(PLEC):c.5024G>A(p.Arg1675Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,585,642 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).
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.5024G>A | p.Arg1675Gln | missense_variant | 31/32 | ENST00000345136.8 | NP_958786.1 | |
PLEC | NM_201378.4 | c.4982G>A | p.Arg1661Gln | missense_variant | 31/32 | ENST00000356346.7 | NP_958780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.5024G>A | p.Arg1675Gln | missense_variant | 31/32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.4982G>A | p.Arg1661Gln | missense_variant | 31/32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.000645 AC: 98AN: 152036Hom.: 2 Cov.: 35
GnomAD3 exomes AF: 0.000653 AC: 131AN: 200596Hom.: 0 AF XY: 0.000625 AC XY: 70AN XY: 111996
GnomAD4 exome AF: 0.00108 AC: 1552AN: 1433492Hom.: 0 Cov.: 68 AF XY: 0.00102 AC XY: 728AN XY: 712342
GnomAD4 genome AF: 0.000644 AC: 98AN: 152150Hom.: 2 Cov.: 35 AF XY: 0.000591 AC XY: 44AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:4Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PLEC: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 27, 2020 | This variant is associated with the following publications: (PMID: 32707200) - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 31, 2019 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 05, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 04, 2024 | Variant summary: PLEC1 c.5105G>A (p.Arg1702Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 1585642 control chromosomes in the gnomAD v4 database, including 2 homozygotes. c.5105G>A has been reported in the literature in one individual affected with posterior segment uveitis (Li_2020). The report does not provide unequivocal conclusions about association of the variant with PLEC1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 3270720). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=1) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign. - |
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 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at