Submissions for variant NM_003119.4(SPG7):c.161A>G (p.Glu54Gly)

gnomAD frequency: 0.00009  dbSNP: rs750617337

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000791714	SCV000930974	uncertain significance	Hereditary spastic paraplegia 7	2025-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 54 of the SPG7 protein (p.Glu54Gly). This variant is present in population databases (rs750617337, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 639021). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SPG7 protein function with a negative predictive value of 95%. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003334009	SCV004041977	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	SPG7: PM2, BP4
Mayo Clinic Laboratories, Mayo Clinic	RCV003334009	SCV005412577	uncertain significance	not provided	2024-06-25	criteria provided, single submitter	clinical testing	BP4