Submissions for variant NM_001177316.2(SLC34A3):c.790G>A (p.Gly264Ser)

gnomAD frequency: 0.00148  dbSNP: rs148072630

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000331619	SCV000337655	likely benign	not specified	2015-11-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000988309	SCV001137977	likely benign	Autosomal recessive hypophosphatemic bone disease	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV001243047	SCV001416179	likely benign	not provided	2024-01-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000331619	SCV003923242	likely benign	not specified	2023-03-21	criteria provided, single submitter	clinical testing	Variant summary: SLC34A3 c.790G>A (p.Gly264Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00097 in 250520 control chromosomes, predominantly at a frequency of 0.0019 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC34A3 causing Hereditary Hypophosphatemic Rickets With Hypercalciuria phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.790G>A in individuals affected with Hereditary Hypophosphatemic Rickets With Hypercalciuria and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx	RCV001243047	SCV003930530	uncertain significance	not provided	2022-12-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000988309	SCV004564132	likely benign	Autosomal recessive hypophosphatemic bone disease	2023-11-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003909968	SCV004721220	likely benign	SLC34A3-related condition	2022-02-25	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).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000331619	SCV001932392	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001243047	SCV001965354	likely benign	not provided		no assertion criteria provided	clinical testing