rs28936695
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000223.4(KRT12):c.386T>C(p.Met129Thr) 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. M129V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000223.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT12 | NM_000223.4 | c.386T>C | p.Met129Thr | missense_variant | 1/8 | ENST00000251643.5 | |
LOC105371777 | XR_934754.3 | n.63+15941A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT12 | ENST00000251643.5 | c.386T>C | p.Met129Thr | missense_variant | 1/8 | 1 | NM_000223.4 | P1 | |
KRT12 | ENST00000647902.1 | c.278T>C | p.Met93Thr | missense_variant | 2/4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10644419, 20577595, 23569037, 18806880, 26788030, 12700042, 17653038, 16900028, 16352477, 19337156) - |
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Corneal dystrophy, Meesmann, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at