rs199843296
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_201384.3(PLEC):c.1969A>T(p.Ser657Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,612,716 control chromosomes in the GnomAD database, including 1 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. S657N) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.1969A>T | p.Ser657Cys | missense_variant | 16/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.1927A>T | p.Ser643Cys | missense_variant | 16/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.1969A>T | p.Ser657Cys | missense_variant | 16/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.1927A>T | p.Ser643Cys | missense_variant | 16/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000862 AC: 131AN: 151978Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000173 AC: 42AN: 242862Hom.: 0 AF XY: 0.000143 AC XY: 19AN XY: 132524
GnomAD4 exome AF: 0.0000911 AC: 133AN: 1460620Hom.: 1 Cov.: 36 AF XY: 0.0000771 AC XY: 56AN XY: 726622
GnomAD4 genome AF: 0.000881 AC: 134AN: 152096Hom.: 0 Cov.: 33 AF XY: 0.000807 AC XY: 60AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 05, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 02, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 31, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.2050A>T (p.S684C) alteration is located in exon 17 (coding exon 16) of the PLEC gene. This alteration results from a A to T substitution at nucleotide position 2050, causing the serine (S) at amino acid position 684 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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 21, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at