ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.4970A>G (p.Asn1657Ser)

gnomAD frequency: 0.00001  dbSNP: rs376207036
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804760 SCV000944684 uncertain significance Hereditary spastic paraplegia 11 2021-09-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1657 of the SPG11 protein (p.Asn1657Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. 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 serine 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.
GeneDx RCV001759538 SCV001996710 uncertain significance not provided 2019-11-06 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 RCV001849107 SCV002105726 uncertain significance Hereditary spastic paraplegia 2018-02-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468056 SCV002763872 uncertain significance Amyotrophic lateral sclerosis type 5 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468057 SCV002763874 uncertain significance Charcot-Marie-Tooth disease axonal type 2X criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000804760 SCV002763875 uncertain significance Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing

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