4-989866-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_022042.4(SLC26A1):c.1073C>T(p.Ser358Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,576,230 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).
Frequency
Consequence
NM_022042.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A1 | NM_022042.4 | c.1073C>T | p.Ser358Leu | missense_variant | 3/3 | ENST00000398516.3 | |
IDUA | NM_000203.5 | c.299+1917G>A | intron_variant | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A1 | ENST00000398516.3 | c.1073C>T | p.Ser358Leu | missense_variant | 3/3 | 1 | NM_022042.4 | P1 | |
IDUA | ENST00000514224.2 | c.299+1917G>A | intron_variant | 2 | NM_000203.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152262Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000280 AC: 52AN: 185846Hom.: 0 AF XY: 0.000239 AC XY: 24AN XY: 100450
GnomAD4 exome AF: 0.000389 AC: 554AN: 1423850Hom.: 0 Cov.: 70 AF XY: 0.000399 AC XY: 281AN XY: 704628
GnomAD4 genome AF: 0.000328 AC: 50AN: 152380Hom.: 0 Cov.: 35 AF XY: 0.000228 AC XY: 17AN XY: 74528
ClinVar
Submissions by phenotype
not provided Pathogenic:2Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2020 | - - |
Pathogenic, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 358 of the SLC26A1 protein (p.Ser358Leu). This variant is present in population databases (rs148832260, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with nephrolithiasis (PMID: 27210743, 30586318). ClinVar contains an entry for this variant (Variation ID: 242375). 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 expected to disrupt SLC26A1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC26A1 function (PMID: 27210743, 36719378). 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. - |
Nephrolithiasis, calcium oxalate Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at