chr17-41582518-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000526.5(KRT14):c.1336C>T(p.Arg446Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000895 in 1,565,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R446S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000526.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT14 | NM_000526.5 | c.1336C>T | p.Arg446Cys | missense_variant | 8/8 | ENST00000167586.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT14 | ENST00000167586.7 | c.1336C>T | p.Arg446Cys | missense_variant | 8/8 | 1 | NM_000526.5 | P1 | |
KRT14 | ENST00000441550.2 | n.844C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000116 AC: 2AN: 171848Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 91214
GnomAD4 exome AF: 0.00000779 AC: 11AN: 1412746Hom.: 0 Cov.: 31 AF XY: 0.00000859 AC XY: 6AN XY: 698146
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 446 of the KRT14 protein (p.Arg446Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KRT14 protein function. This variant has not been reported in the literature in individuals affected with KRT14-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at