rs121912474
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The ENST00000252242.9(KRT5):c.20T>C(p.Val7Ala) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
KRT5
ENST00000252242.9 missense
ENST00000252242.9 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-52520277-A-G is Pathogenic according to our data. Variant chr12-52520277-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 14646.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.22348458). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT5 | NM_000424.4 | c.20T>C | p.Val7Ala | missense_variant | 1/9 | ENST00000252242.9 | NP_000415.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT5 | ENST00000252242.9 | c.20T>C | p.Val7Ala | missense_variant | 1/9 | 1 | NM_000424.4 | ENSP00000252242 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Epidermolysis bullosa simplex 2B, generalized intermediate Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1998 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
A
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;D;D
Sift4G
Benign
T;.;T;T
Polyphen
B;.;.;.
Vest4
MutPred
Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at