rs201820569
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The ENST00000436759.6(PLEC):c.133G>A(p.Gly45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,606,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G45G) has been classified as Likely benign.
Frequency
Consequence
ENST00000436759.6 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 | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_000445.5 | c.133G>A | p.Gly45Ser | missense_variant | 2/33 | ||
PLEC | NM_001410941.1 | c.133G>A | p.Gly45Ser | missense_variant | 2/32 | ||
PLEC | XM_006716588.4 | c.133G>A | p.Gly45Ser | missense_variant | 2/34 | ||
PLEC | XM_047421872.1 | c.133G>A | p.Gly45Ser | missense_variant | 2/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000436759.6 | c.133G>A | p.Gly45Ser | missense_variant | 2/33 | 1 | |||
PLEC | ENST00000528025.6 | c.133G>A | p.Gly45Ser | missense_variant | 1/34 | 5 | |||
PLEC | ENST00000527096.5 | c.133G>A | p.Gly45Ser | missense_variant | 1/32 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000552 AC: 84AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000177 AC: 43AN: 242430Hom.: 0 AF XY: 0.000113 AC XY: 15AN XY: 132470
GnomAD4 exome AF: 0.0000722 AC: 105AN: 1454390Hom.: 0 Cov.: 32 AF XY: 0.0000608 AC XY: 44AN XY: 723866
GnomAD4 genome ? AF: 0.000545 AC: 83AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45AN XY: 74502
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 10, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 14, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2019 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
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 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at