4-9890687-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PP3_ModeratePP5BS1_SupportingBS2
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).
Frequency
Consequence
NM_020041.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
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
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 | 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. - |
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 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2022 | This missense change has been observed in individual(s) with hypouricemia (PMID: 19026395, 24397858, 24940677). 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). This variant is present in population databases (rs121908321, gnomAD 0.1%). ClinVar contains an entry for this variant (Variation ID: 4596). 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"). Experimental studies have shown that this missense change affects SLC2A9 function (PMID: 19026395, 29967582). 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