chr17-41583266-A-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000526.5(KRT14):c.1243T>C(p.Tyr415His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y415C) has been classified as Pathogenic.
Frequency
Consequence
NM_000526.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT14 | NM_000526.5 | c.1243T>C | p.Tyr415His | missense_variant | 6/8 | ENST00000167586.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT14 | ENST00000167586.7 | c.1243T>C | p.Tyr415His | missense_variant | 6/8 | 1 | NM_000526.5 | P1 | |
KRT14 | ENST00000441550.2 | n.190T>C | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
KRT14 | ENST00000476662.1 | n.693T>C | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2015 | The Y415H missense variant in the KRT14 gene has been reported previously in two patients withEpidermolysis Bullosa Simplex (EBS), one with a milder form of the disorder and one with severe generalizedblistering (Hut et al., 2000; Rugg et al., 2000). Y415H was not observed in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. This substitution is located at a highly conserved position in thehelix termination motif of the KRT14 gene where a tyrosine residue is also present in other filament proteins(Rugg et al., 2000). We interpret Y415H as a pathogenic variant. - |
Epidermolysis bullosa simplex, Koebner type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at