ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1728G>T (p.Glu576Asp)

dbSNP: rs1060502225
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001288791 SCV001476150 uncertain significance not provided 2020-03-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001871722 SCV002224590 uncertain significance Hereditary spastic paraplegia 4 2023-04-22 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 994981). This variant has not been reported in the literature in individuals affected with SPAST-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 576 of the SPAST protein (p.Glu576Asp). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon.

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