Submissions for variant NM_001379110.1(SLC9A6):c.1083G>A (p.Leu361=)

gnomAD frequency: 0.00022  dbSNP: rs151178361

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV001083801	SCV004808298	benign	Christianson syndrome	2024-02-23	reviewed by expert panel	curation	The allele frequency of the p.Leu381= variant in SLC9A6 (NM_006359.2) is 0.024% in European (Non-Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The silent p.Leu381= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). The p.Leu381= variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2_strong). The p.Leu381= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Leu381= variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BS1, BP4, BP7, BS2_strong, BP5_strong).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083801	SCV000647050	benign	Christianson syndrome	2023-09-04	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000594833	SCV000701568	uncertain significance	not provided	2016-10-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000720971	SCV000851855	likely benign	History of neurodevelopmental disorder	2013-10-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
GeneDx	RCV000594833	SCV001885517	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000594833	SCV004165691	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	SLC9A6: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003942821	SCV004757503	likely benign	SLC9A6-related disorder	2023-11-27	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).