Submissions for variant NM_014855.3(AP5Z1):c.849C>T (p.Ala283=)

gnomAD frequency: 0.00060  dbSNP: rs572271008

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226846	SCV000290024	likely benign	Hereditary spastic paraplegia 48	2024-10-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000226846	SCV001321536	uncertain significance	Hereditary spastic paraplegia 48	2018-03-02	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics	RCV001288787	SCV001476144	likely benign	not specified	2024-08-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847988	SCV002106213	uncertain significance	Hereditary spastic paraplegia	2020-08-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003430791	SCV004158843	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	AP5Z1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003967657	SCV004787757	likely benign	AP5Z1-related disorder	2019-02-22	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).