chrX-37686137-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021083.4(XK):c.176A>G(p.His59Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,062 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic 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. H59Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_021083.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XK | NM_021083.4 | c.176A>G | p.His59Arg | missense_variant | 1/3 | ENST00000378616.5 | |
XK | XM_011543978.4 | c.176A>G | p.His59Arg | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XK | ENST00000378616.5 | c.176A>G | p.His59Arg | missense_variant | 1/3 | 1 | NM_021083.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1096062Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1AN XY: 361708
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2022 | This variant has not been reported in the literature in individuals affected with XK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 59 of the XK protein (p.His59Arg). ClinVar contains an entry for this variant (Variation ID: 1715048). 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 not expected to disrupt XK protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at