chr8-143916836-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_201384.3(PLEC):c.12985C>T(p.Arg4329Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,612,668 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. R4329H) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.12985C>T | p.Arg4329Cys | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.12943C>T | p.Arg4315Cys | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.12985C>T | p.Arg4329Cys | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.12943C>T | p.Arg4315Cys | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.0000988 AC: 15AN: 151868Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000185 AC: 46AN: 248312Hom.: 1 AF XY: 0.000207 AC XY: 28AN XY: 135146
GnomAD4 exome AF: 0.000103 AC: 150AN: 1460682Hom.: 2 Cov.: 45 AF XY: 0.000136 AC XY: 99AN XY: 726658
GnomAD4 genome AF: 0.0000921 AC: 14AN: 151986Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74296
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 30, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.13066C>T (p.R4356C) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a C to T substitution at nucleotide position 13066, causing the arginine (R) at amino acid position 4356 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 | Dec 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at