ClinVar Miner

Submissions for variant NM_015087.5(SPART):c.862T>C (p.Cys288Arg)

gnomAD frequency: 0.00006  dbSNP: rs771147428
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520198 SCV000618644 uncertain significance not provided 2017-06-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SPG20 gene. The C288R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C288R variant is observed in 3/66,524 (0.005%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The C288R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, Arginine is observed at this position in evolution. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848916 SCV002105808 uncertain significance Hereditary spastic paraplegia 2016-12-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000520198 SCV003796476 uncertain significance not provided 2022-04-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 288 of the SPART protein (p.Cys288Arg). This variant is present in population databases (rs771147428, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SPART-related conditions. ClinVar contains an entry for this variant (Variation ID: 450101). 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"). 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.
Ambry Genetics RCV004023554 SCV004957369 uncertain significance Inborn genetic diseases 2022-04-13 criteria provided, single submitter clinical testing The c.862T>C (p.C288R) alteration is located in exon 3 (coding exon 2) of the SPG20 gene. This alteration results from a T to C substitution at nucleotide position 862, causing the cysteine (C) at amino acid position 288 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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