ClinVar Miner

Submissions for variant NM_003334.4(UBA1):c.2842T>G (p.Tyr948Asp)

gnomAD frequency: 0.00012  dbSNP: rs781929195
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002040387 SCV002299381 uncertain significance Infantile-onset X-linked spinal muscular atrophy 2021-04-10 criteria provided, single submitter clinical testing 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. 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"). This variant has not been reported in the literature in individuals with UBA1-related conditions. This variant is present in population databases (rs781929195, ExAC 0.04%). This sequence change replaces tyrosine with aspartic acid at codon 948 of the UBA1 protein (p.Tyr948Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid.
Ambry Genetics RCV002441204 SCV002748498 uncertain significance Inborn genetic diseases 2020-06-01 criteria provided, single submitter clinical testing The p.Y948D variant (also known as c.2842T>G), located in coding exon 23 of the UBA1 gene, results from a T to G substitution at nucleotide position 2842. The tyrosine at codon 948 is replaced by aspartic acid, an amino acid with highly dissimilar properties. Based on data from gnomAD, the c.2842T>G variant has an overall frequency of 0.004% (8/205,057) of total alleles studied. The highest observed frequency was 0.04% (8/18,861) in the African sub-population, with no hemizygotes observed. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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