rs782085661
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_201384.3(PLEC):c.9713C>T(p.Pro3238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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. P3238P) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.9713C>T | p.Pro3238Leu | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.9671C>T | p.Pro3224Leu | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.9713C>T | p.Pro3238Leu | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.9671C>T | p.Pro3224Leu | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 247796Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134946
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1460726Hom.: 0 Cov.: 73 AF XY: 0.0000303 AC XY: 22AN XY: 726652
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 390991). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs782085661, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3265 of the PLEC protein (p.Pro3265Leu). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 30, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 23, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at