rs190789703
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_201384.3(PLEC):c.13509C>T(p.Arg4503Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000609 in 1,582,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_201384.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.13509C>T | p.Arg4503Arg | synonymous_variant | Exon 32 of 32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.13467C>T | p.Arg4489Arg | synonymous_variant | Exon 32 of 32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.000526 AC: 80AN: 152042Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000439 AC: 83AN: 189050Hom.: 0 AF XY: 0.000427 AC XY: 45AN XY: 105500
GnomAD4 exome AF: 0.000618 AC: 884AN: 1429940Hom.: 0 Cov.: 36 AF XY: 0.000588 AC XY: 417AN XY: 709702
GnomAD4 genome AF: 0.000526 AC: 80AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
PLEC: BP4, BP7 -
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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
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PLEC-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at