rs187648086
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_201384.3(PLEC):c.3731T>G(p.Val1244Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,600,688 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.3731T>G | p.Val1244Gly | missense_variant | 27/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.3689T>G | p.Val1230Gly | missense_variant | 27/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.3731T>G | p.Val1244Gly | missense_variant | 27/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.3689T>G | p.Val1230Gly | missense_variant | 27/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000889 AC: 135AN: 151806Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000711 AC: 162AN: 227980Hom.: 1 AF XY: 0.000643 AC XY: 81AN XY: 125910
GnomAD4 exome AF: 0.00161 AC: 2327AN: 1448764Hom.: 4 Cov.: 50 AF XY: 0.00150 AC XY: 1079AN XY: 721052
GnomAD4 genome ? AF: 0.000889 AC: 135AN: 151924Hom.: 0 Cov.: 35 AF XY: 0.000848 AC XY: 63AN XY: 74282
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 06, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | PLEC: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 02, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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