rs149622425
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033409.4(SLC52A3):āc.203G>Cā(p.Cys68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,582,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_033409.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.203G>C | p.Cys68Ser | missense_variant | 2/5 | ENST00000645534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.203G>C | p.Cys68Ser | missense_variant | 2/5 | NM_033409.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152122Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000810 AC: 16AN: 197594Hom.: 0 AF XY: 0.0000855 AC XY: 9AN XY: 105258
GnomAD4 exome AF: 0.000222 AC: 318AN: 1430014Hom.: 0 Cov.: 36 AF XY: 0.000225 AC XY: 159AN XY: 708040
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152122Hom.: 0 Cov.: 31 AF XY: 0.0000808 AC XY: 6AN XY: 74290
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2022 | The p.C68S variant (also known as c.203G>C), located in coding exon 1 of the SLC52A3 gene, results from a G to C substitution at nucleotide position 203. The cysteine at codon 68 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Brown-Vialetto-van Laere syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 68 of the SLC52A3 protein (p.Cys68Ser). This variant is present in population databases (rs149622425, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 452583). 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 not expected to disrupt SLC52A3 protein function with a negative predictive value of 80%. 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