Submissions for variant NM_014855.3(AP5Z1):c.1033C>T (p.Arg345Ter)

gnomAD frequency: 0.00004  dbSNP: rs762066700

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220110	SCV001392083	pathogenic	Hereditary spastic paraplegia 48	2022-09-07	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 948785). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with complicated spastic paraplegia (PMID: 27606357). This variant is present in population databases (rs762066700, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg345*) in the AP5Z1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AP5Z1 are known to be pathogenic (PMID: 20613862, 27606357).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847197	SCV002106050	pathogenic	Hereditary spastic paraplegia	2021-07-09	criteria provided, single submitter	clinical testing
Centre for Clinical Genetics and Genomic Diagnostics, Zealand University Hospital	RCV004720800	SCV005328405	pathogenic	not provided	2023-06-15	criteria provided, single submitter	clinical testing	Found in putative compoúnd heterozygous state with another AP5Z1 variant.