8-143933310-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_201384.3(PLEC):c.1305G>A(p.Ala435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,612,746 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). Synonymous variant affecting the same amino acid position (i.e. A435A) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.1305G>A | p.Ala435= | synonymous_variant | 13/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.1263G>A | p.Ala421= | synonymous_variant | 13/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.1305G>A | p.Ala435= | synonymous_variant | 13/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.1263G>A | p.Ala421= | synonymous_variant | 13/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000133 AC: 33AN: 248296Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135170
GnomAD4 exome AF: 0.000200 AC: 292AN: 1460556Hom.: 0 Cov.: 59 AF XY: 0.000204 AC XY: 148AN XY: 726606
GnomAD4 genome AF: 0.000138 AC: 21AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 28, 2016 | - - |
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 14, 2023 | - - |
PLEC-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2022 | 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