Submissions for variant NM_001776.6(ENTPD1):c.1333G>C (p.Gly445Arg)

gnomAD frequency: 0.00046  dbSNP: rs145994698

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000652016	SCV000773875	uncertain significance	Hereditary spastic paraplegia 64	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 445 of the ENTPD1 protein (p.Gly445Arg). This variant is present in population databases (rs145994698, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ENTPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 541701). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001849031	SCV002104633	uncertain significance	Hereditary spastic paraplegia	2022-01-17	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004692041	SCV005190953	uncertain significance	not provided		criteria provided, single submitter	not provided