ClinVar Miner

Submissions for variant NM_015915.5(ATL1):c.1546G>A (p.Asp516Asn)

dbSNP: rs776441162
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000696450 SCV000825013 uncertain significance Hereditary spastic paraplegia 3A 2018-03-22 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATL1-related disease. This variant is present in population databases (rs776441162, ExAC 0.002%). This sequence change replaces aspartic acid with asparagine at codon 516 of the ATL1 protein (p.Asp516Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755830 SCV000883419 uncertain significance not provided 2018-03-07 criteria provided, single submitter clinical testing The ATL1 c.1546G>A; p.Asp516Asn variant (rs776441162), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.0004% (identified on 1 out of 245,802 chromosomes). The aspartic acid at position 516 is highly conserved, considering 11 species, and computational analyses of the effects of the p.Asp516Asn variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Asp516Asn variant cannot be determined with certainty.

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