17-41582508-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000526.5(KRT14):c.1346G>A(p.Arg449His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,104 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 (★★).
Frequency
Consequence
NM_000526.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000561 AC: 1AN: 178362Hom.: 0 AF XY: 0.0000105 AC XY: 1AN XY: 94794
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000565 AC: 8AN: 1416552Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2AN XY: 700308
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74288
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1346G>A (p.R449H) alteration is located in exon 8 (coding exon 8) of the KRT14 gene. This alteration results from a G to A substitution at nucleotide position 1346, causing the arginine (R) at amino acid position 449 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 449 of the KRT14 protein (p.Arg449His). 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. This variant has not been reported in the literature in individuals affected with KRT14-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at