12-52519125-G-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000424.4(KRT5):c.591C>A(p.Asp197Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,610,082 control chromosomes in the GnomAD database, including 55,915 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000424.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT5 | NM_000424.4 | c.591C>A | p.Asp197Glu | missense_variant | 2/9 | ENST00000252242.9 | NP_000415.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT5 | ENST00000252242.9 | c.591C>A | p.Asp197Glu | missense_variant | 2/9 | 1 | NM_000424.4 | ENSP00000252242.4 |
Frequencies
GnomAD3 genomes AF: 0.230 AC: 34888AN: 151888Hom.: 4479 Cov.: 32
GnomAD3 exomes AF: 0.245 AC: 60185AN: 245436Hom.: 7471 AF XY: 0.244 AC XY: 32447AN XY: 132766
GnomAD4 exome AF: 0.265 AC: 386047AN: 1458076Hom.: 51436 Cov.: 80 AF XY: 0.263 AC XY: 190850AN XY: 725542
GnomAD4 genome AF: 0.230 AC: 34886AN: 152006Hom.: 4479 Cov.: 32 AF XY: 0.226 AC XY: 16806AN XY: 74292
ClinVar
Submissions by phenotype
not provided Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 31965605, 19578363) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Epidermolysis bullosa simplex Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at