rs121908322
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM5PP3_ModerateBP6
The NM_020041.3(SLC2A9):c.592C>T(p.Arg198Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R198H) has been classified as Pathogenic.
Frequency
Consequence
NM_020041.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A9 | NM_020041.3 | c.592C>T | p.Arg198Cys | missense_variant | 5/12 | ENST00000264784.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A9 | ENST00000264784.8 | c.592C>T | p.Arg198Cys | missense_variant | 5/12 | 1 | NM_020041.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250486Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135378
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461862Hom.: 0 Cov.: 63 AF XY: 0.0000303 AC XY: 22AN XY: 727236
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74436
ClinVar
Submissions by phenotype
Hypouricemia, renal, 2 Pathogenic:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2008 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2021 | 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. Experimental studies have shown that this missense change affects SLC2A9 function (PMID: 19026395, 22132964, 29967582). 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 4597). This missense change has been observed in individual(s) with hypouricemia although a second variant was not observed (PMID: 19026395). This variant is present in population databases (rs121908322, ExAC 0.03%). This sequence change replaces arginine with cysteine at codon 198 of the SLC2A9 protein (p.Arg198Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at