Submissions for variant NM_014855.3(AP5Z1):c.1322G>A (p.Trp441Ter)

gnomAD frequency: 0.00009  dbSNP: rs373919408

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000416330	SCV000650091	pathogenic	Hereditary spastic paraplegia 48	2023-08-02	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 375313). This premature translational stop signal has been observed in individual(s) with spastic paraplegia (PMID: 24833714). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Trp441*) 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	RCV001848739	SCV002106133	pathogenic	Hereditary spastic paraplegia	2018-12-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000416330	SCV003835129	pathogenic	Hereditary spastic paraplegia 48	2021-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003422385	SCV004158849	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	AP5Z1: PVS1, PM2
OMIM	RCV000416330	SCV000494085	pathogenic	Hereditary spastic paraplegia 48	2017-01-26	no assertion criteria provided	literature only