ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.847G>T (p.Asp283Tyr)

gnomAD frequency: 0.00001  dbSNP: rs199476386
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000058982 SCV000110814 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing
Counsyl RCV000668155 SCV000792709 uncertain significance Metachromatic leukodystrophy 2017-07-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668155 SCV001226680 pathogenic Metachromatic leukodystrophy 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 283 of the ARSA protein (p.Asp283Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with metachromatic leukodystrophy (PMID: 10533072). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as AKA Asp281Tyr. ClinVar contains an entry for this variant (Variation ID: 68151). 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 ARSA protein function with a positive predictive value of 95%. This variant disrupts the p.Asp283 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been observed in individuals with ARSA-related conditions (PMID: 28670130, 30057904, 31694723), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000058982 SCV001880044 uncertain significance not provided 2021-01-13 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000058982 SCV000090503 not provided not provided no assertion provided not provided

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