chr12-52675216-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_006121.4(KRT1):c.1912A>T(p.Thr638Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T638A) has been classified as Likely benign.
Frequency
Consequence
NM_006121.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT1 | NM_006121.4 | c.1912A>T | p.Thr638Ser | missense_variant | 9/9 | ENST00000252244.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT1 | ENST00000252244.3 | c.1912A>T | p.Thr638Ser | missense_variant | 9/9 | 1 | NM_006121.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250926Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135736
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461550Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 727066
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Epidermolytic hyperkeratosis 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genomics Laboratory, Washington University in St. Louis | Sep 22, 2023 | The KRT1 c.1912A>T (p.Thr638Ser) variant was identified at near heterozygous allelic fraction and to our knowledge, it has not been reported in the medical literature. This variant is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors suggest that the variant does not impact KRT1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), KRT1 c.1912A>T (p.Thr638Ser) is classified as being of uncertain significance at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at