Submissions for variant NM_014946.4(SPAST):c.131C>T (p.Ser44Leu)

gnomAD frequency: 0.00521  dbSNP: rs121908515

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000197924	SCV000253525	likely benign	Hereditary spastic paraplegia 4	2024-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000368675	SCV000340650	benign	not specified	2016-04-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000197924	SCV000430098	benign	Hereditary spastic paraplegia 4	2018-03-06	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000440604	SCV000510640	benign	not provided	2017-02-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000368675	SCV000514731	benign	not specified	2016-08-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000197924	SCV000743203	likely benign	Hereditary spastic paraplegia 4	2014-10-09	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000368675	SCV000844073	benign	not specified	2020-05-12	criteria provided, single submitter	clinical testing
Mendelics	RCV000197924	SCV001135650	benign	Hereditary spastic paraplegia 4	2019-05-28	criteria provided, single submitter	clinical testing
Neurogenetics Research Program, University of Adelaide	RCV001794433	SCV001737578	other	Cerebral palsy	2021-06-10	criteria provided, single submitter	research	Modifier of age of onset/severity of SPG4 (PMID: 30476002, PMID: 17916079) in carrier of paternally inherited SPAST deletion.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000197924	SCV001976883	risk factor	Hereditary spastic paraplegia 4	2021-10-06	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847587	SCV002105593	benign	Hereditary spastic paraplegia	2020-05-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000440604	SCV002498541	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	SPAST: PP3, BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV000197924	SCV002796289	likely benign	Hereditary spastic paraplegia 4	2022-01-13	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000440604	SCV005263348	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000006025	SCV000026207	risk factor	Spastic paraplegia 4, modifier of	2006-07-11	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000197924	SCV000734195	likely benign	Hereditary spastic paraplegia 4		no assertion criteria provided	clinical testing
GeneReviews	RCV000197924	SCV000987269	not provided	Hereditary spastic paraplegia 4		no assertion provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000440604	SCV001957310	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003924803	SCV004743775	benign	SPAST-related disorder	2019-05-22	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).