Submissions for variant NM_152296.5(ATP1A3):c.6+3A>G

gnomAD frequency: 0.00016  dbSNP: rs369853936

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000350142	SCV000413475	benign	Alternating hemiplegia of childhood 2	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000385973	SCV000413476	benign	Dystonia 12	2018-01-12	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.
Athena Diagnostics	RCV000518390	SCV000612450	benign	not specified	2017-07-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000385973	SCV000645414	likely benign	Dystonia 12	2024-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000858874	SCV001151941	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	ATP1A3: BP4, BS1
GeneDx	RCV000858874	SCV001849927	benign	not provided	2019-05-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000350142	SCV002539107	benign	Alternating hemiplegia of childhood 2	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002259894	SCV002539108	benign	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002259895	SCV002539109	benign	Developmental and epileptic encephalopathy 99	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000385973	SCV002539111	benign	Dystonia 12	2021-12-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003243084	SCV003950315	likely benign	Inborn genetic diseases	2023-04-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
PreventionGenetics, part of Exact Sciences	RCV004549742	SCV004746329	likely benign	ATP1A3-related disorder	2023-11-09	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).