Submissions for variant NM_003052.5(SLC34A1):c.1006+1G>A

gnomAD frequency: 0.00001  dbSNP: rs200095793

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000354958	SCV000330724	pathogenic	not provided	2021-06-22	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30778725, 26047794, 29959532, 27535533)
Illumina Laboratory Services, Illumina	RCV001157728	SCV001319326	uncertain significance	Hypophosphatemic nephrolithiasis/osteoporosis 1	2017-10-05	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV000354958	SCV003439298	likely pathogenic	not provided	2023-07-20	criteria provided, single submitter	clinical testing	Disruption of this splice site has been observed in individual(s) with autosomal recessive hypercalcemia (PMID: 26047794). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 234928). This variant is present in population databases (rs200095793, gnomAD 0.03%). This sequence change affects a donor splice site in intron 9 of the SLC34A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC34A1 are known to be pathogenic (PMID: 26047794).
OMIM	RCV000223671	SCV000280017	pathogenic	Hypercalcemia, infantile, 2	2016-10-06	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000354958	SCV001928562	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000354958	SCV001957380	pathogenic	not provided		no assertion criteria provided	clinical testing