rs752218005
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_033409.4(SLC52A3):c.935C>T(p.Ala312Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,094 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).
Frequency
Consequence
NM_033409.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.935C>T | p.Ala312Val | 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.935C>T | p.Ala312Val | missense_variant | 3/5 | NM_033409.4 | ENSP00000494193 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251430Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135896
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727236
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Brown-Vialetto-van Laere syndrome 1 Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 14, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 312 of the SLC52A3 protein (p.Ala312Val). This variant is present in population databases (rs752218005, gnomAD 0.003%). This missense change has been observed in individual(s) with Brown–Vialetto–Van Laere syndrome (PMID: 22718020, 33189404). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 210021). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 33189404, 27702554, 22718020, 23107375) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at