rs370718326
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_033409.4(SLC52A3):c.319G>A(p.Ala107Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,608,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A107A) has been classified as Benign.
Frequency
Consequence
NM_033409.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.319G>A | p.Ala107Thr | missense_variant | 2/5 | ENST00000645534.1 | NP_212134.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.319G>A | p.Ala107Thr | missense_variant | 2/5 | NM_033409.4 | ENSP00000494193.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152126Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000334 AC: 8AN: 239194Hom.: 0 AF XY: 0.0000309 AC XY: 4AN XY: 129384
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1456850Hom.: 0 Cov.: 37 AF XY: 0.0000207 AC XY: 15AN XY: 724270
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152126Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.319G>A (p.A107T) alteration is located in exon 2 (coding exon 1) of the SLC52A3 gene. This alteration results from a G to A substitution at nucleotide position 319, causing the alanine (A) at amino acid position 107 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Brown-Vialetto-van Laere syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 18, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 107 of the SLC52A3 protein (p.Ala107Thr). This variant is present in population databases (rs370718326, gnomAD 0.01%). 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: 476608). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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