ClinVar Miner

Submissions for variant NM_015087.5(SPART):c.1139G>A (p.Arg380His)

gnomAD frequency: 0.00002  dbSNP: rs956021462
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426352 SCV000535877 uncertain significance not provided 2017-01-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SPG20 gene. The R380H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R380H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R380H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000426352 SCV000960949 uncertain significance not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 380 of the SPART protein (p.Arg380His). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 392586). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV004965459 SCV005509190 uncertain significance Inborn genetic diseases 2024-07-25 criteria provided, single submitter clinical testing The c.1139G>A (p.R380H) alteration is located in exon 4 (coding exon 3) of the SPG20 gene. This alteration results from a G to A substitution at nucleotide position 1139, causing the arginine (R) at amino acid position 380 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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