rs201990981
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033409.4(SLC52A3):c.890C>T(p.Pro297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,016 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 (★★).
Frequency
Consequence
NM_033409.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.890C>T | p.Pro297Leu | missense_variant | 3/5 | ENST00000645534.1 | NP_212134.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.890C>T | p.Pro297Leu | missense_variant | 3/5 | NM_033409.4 | ENSP00000494193.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251318Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135856
GnomAD4 exome AF: 0.000120 AC: 176AN: 1461848Hom.: 0 Cov.: 35 AF XY: 0.000129 AC XY: 94AN XY: 727236
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2019 | The p.P297L variant (also known as c.890C>T), located in coding exon 2 of the SLC52A3 gene, results from a C to T substitution at nucleotide position 890. The proline at codon 297 is replaced by leucine, an amino acid with similar properties. This amino acid position is poorly 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. - |
Brown-Vialetto-van Laere syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2021 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 297 of the SLC52A3 protein (p.Pro297Leu). This variant is present in population databases (rs201990981, 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: 570161). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. - |
Progressive bulbar palsy of childhood;C0796274:Brown-Vialetto-van Laere syndrome 1 Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 02-03-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at