rs141953803
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001363118.2(SLC52A2):c.478G>A(p.Val160Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,613,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V160G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001363118.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A2 | NM_001363118.2 | c.478G>A | p.Val160Met | missense_variant | 3/5 | ENST00000643944.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A2 | ENST00000643944.2 | c.478G>A | p.Val160Met | missense_variant | 3/5 | NM_001363118.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000758 AC: 19AN: 250804Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135726
GnomAD4 exome AF: 0.000132 AC: 193AN: 1460878Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 726740
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
Brown-Vialetto-van Laere syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 160 of the SLC52A2 protein (p.Val160Met). This variant is present in population databases (rs141953803, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SLC52A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 540428). 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 SLC52A2 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2024 | The c.478G>A (p.V160M) alteration is located in exon 3 (coding exon 2) of the SLC52A2 gene. This alteration results from a G to A substitution at nucleotide position 478, causing the valine (V) at amino acid position 160 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at