ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.1042G>A (p.Ala348Thr)

gnomAD frequency: 0.00001  dbSNP: rs752735865
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001201984 SCV001373079 uncertain significance Adenylosuccinate lyase deficiency 2023-05-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 348 of the ADSL protein (p.Ala348Thr). This variant is present in population databases (rs752735865, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 933713). 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 ADSL 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.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV001201984 SCV004046994 uncertain significance Adenylosuccinate lyase deficiency criteria provided, single submitter clinical testing The missense c.1042G>A (p.Ala348Thr) variant in ADSL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.001% in the gnomAD and novel in 1000 genome database. This variant has been reported to the ClinVar database as uncertain significance. The amino acid Ala at position 348 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by PolyPhen2 and the residue is conserved across species. The amino acid change p.Ala348Thr in ADSL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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