rs139024319
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_022042.4(SLC26A1):c.554C>T(p.Thr185Met) variant causes a missense change. The variant allele was found at a frequency of 0.000294 in 1,552,418 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). Synonymous variant affecting the same amino acid position (i.e. T185T) has been classified as Likely benign.
Frequency
Consequence
NM_022042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A1 | NM_022042.4 | c.554C>T | p.Thr185Met | missense_variant | 2/3 | ENST00000398516.3 | |
IDUA | NM_000203.5 | c.299+3201G>A | intron_variant | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A1 | ENST00000398516.3 | c.554C>T | p.Thr185Met | missense_variant | 2/3 | 1 | NM_022042.4 | P1 | |
IDUA | ENST00000514224.2 | c.299+3201G>A | intron_variant | 2 | NM_000203.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152208Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000254 AC: 52AN: 204950Hom.: 0 AF XY: 0.000211 AC XY: 23AN XY: 109000
GnomAD4 exome AF: 0.000306 AC: 429AN: 1400092Hom.: 0 Cov.: 32 AF XY: 0.000313 AC XY: 215AN XY: 687962
GnomAD4 genome AF: 0.000184 AC: 28AN: 152326Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74484
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 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 185 of the SLC26A1 protein (p.Thr185Met). This variant is present in population databases (rs139024319, gnomAD 0.04%). This missense change has been observed in individual(s) with nephrolithiasis (PMID: 27210743, 30586318). ClinVar contains an entry for this variant (Variation ID: 242374). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC26A1 protein function. 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. - |
Likely pathogenic, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
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