4-9890687-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP3_ModeratePP5BS2
The NM_020041.3(SLC2A9):c.1138C>T(p.Arg380Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,614,078 control chromosomes in the GnomAD database, including 2 homozygotes. 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. R380Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_020041.3 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 |
---|---|---|---|---|---|---|---|
SLC2A9 | NM_020041.3 | c.1138C>T | p.Arg380Trp | missense_variant | 9/12 | ENST00000264784.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A9 | ENST00000264784.8 | c.1138C>T | p.Arg380Trp | missense_variant | 9/12 | 1 | NM_020041.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251204Hom.: 0 AF XY: 0.000317 AC XY: 43AN XY: 135772
GnomAD4 exome AF: 0.000114 AC: 166AN: 1461854Hom.: 2 Cov.: 31 AF XY: 0.000168 AC XY: 122AN XY: 727226
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74412
ClinVar
Submissions by phenotype
Hypouricemia, renal, 2 Pathogenic:4Uncertain:1
Likely pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 19, 2023 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | Aug 25, 2014 | Our laboratory reported dual molecular diagnoses in SLC2A9 (NM_020041.2, c.1138C>T) and ETHE1 (homozygous deletion) in one individual with reported features that include hypotonia, retinal visual abnormalities, and nephrotic syndrome. The SLC2A9 variant has been previously reported as disease-causing (PMID 19026395, 24397858, 22132964) and was found in one other individual: a 10-year-old male with autism spectrum, tics, macrocephaly. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | 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, 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: 4596). This missense change has been observed in individual(s) with hypouricemia (PMID: 19026395, 24397858, 24940677). This variant is present in population databases (rs121908321, gnomAD 0.1%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 380 of the SLC2A9 protein (p.Arg380Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at