rs376936955
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_201384.3(PLEC):c.2613-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,609,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_201384.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201378.4 | c.2571-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000356346.7 | NP_958780.1 | |||
PLEC | NM_201384.3 | c.2613-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000345136.8 | NP_958786.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.2613-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_201384.3 | ENSP00000344848 | ||||
PLEC | ENST00000356346.7 | c.2571-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_201378.4 | ENSP00000348702 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000622 AC: 15AN: 241246Hom.: 0 AF XY: 0.0000831 AC XY: 11AN XY: 132366
GnomAD4 exome AF: 0.0000398 AC: 58AN: 1457246Hom.: 0 Cov.: 64 AF XY: 0.0000621 AC XY: 45AN XY: 725168
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74348
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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | - - |
PLEC-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | 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