ClinVar Miner

Submissions for variant NM_033409.4(SLC52A3):c.106G>A (p.Glu36Lys)

gnomAD frequency: 0.00001  dbSNP: rs267606686
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000000166 SCV000775598 uncertain significance Brown-Vialetto-van Laere syndrome 1 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 36 of the SLC52A3 protein (p.Glu36Lys). This variant is present in population databases (rs267606686, gnomAD 0.003%). This missense change has been observed in individual(s) with Brown-Vialetto-Van Laere syndrome (BVVLS) (PMID: 20206331, 23688382, 29053833, 29950502). ClinVar contains an entry for this variant (Variation ID: 143). 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 expected to disrupt SLC52A3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC52A3 function (PMID: 22273710). 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.
GeneDx RCV001560824 SCV001783309 likely pathogenic not provided 2021-11-09 criteria provided, single submitter clinical testing Identified in a patient with BVVLS who presented at 5 years old with sensorineural hearing loss, followed by speech difficulties, weakness, and respiratory issues; no second variant was identified (Malafronte et al., 2013); Published functional studies demonstrate reduced riboflavin uptake (Nabokina et al., 2012); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26072523, 22273710, 29950502, 23688382, 20206331, 23107375, 23506902, 29053833, 34662687)
Mendelics RCV002247227 SCV002519783 pathogenic Progressive bulbar palsy of childhood 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV000000166 SCV000020309 pathogenic Brown-Vialetto-van Laere syndrome 1 2010-03-12 no assertion criteria provided literature only
GeneReviews RCV000000166 SCV000246209 not provided Brown-Vialetto-van Laere syndrome 1 no assertion provided literature only

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