rs121912475
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_000424.4(KRT5):c.556G>T(p.Val186Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V186M) has been classified as Pathogenic.
Frequency
Consequence
NM_000424.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT5 | NM_000424.4 | c.556G>T | p.Val186Leu | missense_variant, splice_region_variant | 2/9 | ENST00000252242.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT5 | ENST00000252242.9 | c.556G>T | p.Val186Leu | missense_variant, splice_region_variant | 2/9 | 1 | NM_000424.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 38
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Epidermolysis bullosa simplex Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Biomedical Innovation Departament, CIEMAT | May 04, 2015 | - - |
Epidermolysis bullosa simplex 2B, generalized intermediate Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2001 | - - |
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at