Submissions for variant NM_000478.6(ALPL):c.818C>T (p.Thr273Met)

gnomAD frequency: 0.00106  dbSNP: rs148405563

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000710516	SCV000342299	uncertain significance	not provided	2016-05-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000263557	SCV000354303	benign	Hypophosphatasia	2018-01-13	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.
GeneDx	RCV000710516	SCV000566451	likely benign	not provided	2021-02-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21956185, 27042741, 30564332, 32803091)
Athena Diagnostics Inc	RCV000710516	SCV000840754	benign	not provided	2017-09-30	criteria provided, single submitter	clinical testing
Invitae	RCV000710516	SCV001110181	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820834	SCV002066752	likely benign	not specified	2021-11-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519300	SCV003682748	benign	Inborn genetic diseases	2022-01-11	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000710516	SCV004123405	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	ALPL: BS2
JKU Lab, Dept of Paediatrics, Johannes Kepler University	RCV000263557	SCV004174863	uncertain significance	Hypophosphatasia	2022-10-19	criteria provided, single submitter	clinical testing	Further details and the ACMG criteria applied can be looked up in the ALPL gene variant database. https://alplmutationdatabase.jku.at/
PreventionGenetics, part of Exact Sciences	RCV003957495	SCV004774190	likely benign	ALPL-related condition	2024-02-02	criteria provided, single submitter	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).
Natera, Inc.	RCV000263557	SCV001463897	benign	Hypophosphatasia	2020-01-11	no assertion criteria provided	clinical testing