ClinVar Miner

Submissions for variant NM_016630.7(SPG21):c.862A>G (p.Met288Val)

gnomAD frequency: 0.00005  dbSNP: rs371753104
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000695209 SCV000823694 uncertain significance Mast syndrome 2022-03-29 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 288 of the SPG21 protein (p.Met288Val). This variant is present in population databases (rs371753104, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SPG21-related conditions. ClinVar contains an entry for this variant (Variation ID: 573515). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV001766499 SCV001998723 uncertain significance not provided 2019-09-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001849061 SCV002105829 uncertain significance Hereditary spastic paraplegia 2016-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV004025234 SCV003700390 uncertain significance not specified 2022-08-22 criteria provided, single submitter clinical testing The c.862A>G (p.M288V) alteration is located in exon 9 (coding exon 8) of the SPG21 gene. This alteration results from a A to G substitution at nucleotide position 862, causing the methionine (M) at amino acid position 288 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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