8-143933998-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_201384.3(PLEC):c.1263G>A(p.Ser421=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S421S) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.1263G>A | p.Ser421= | splice_region_variant, synonymous_variant | 12/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.1221G>A | p.Ser407= | splice_region_variant, synonymous_variant | 12/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.1263G>A | p.Ser421= | splice_region_variant, synonymous_variant | 12/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.1221G>A | p.Ser407= | splice_region_variant, synonymous_variant | 12/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456702Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 724560
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Epidermolysis bullosa simplex 5C, with pyloric atresia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2005 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at