Submissions for variant NM_012434.5(SLC17A5):c.819+1G>A

dbSNP: rs1057517028

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000412283	SCV000486624	likely pathogenic	Salla disease	2016-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000437560	SCV000517212	pathogenic	not provided	2020-11-11	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Identified in a patient with clinical features consistent with SLC17A5-related disorder in published literature (Barmherzig et al., 2017; Lionel et al., 2018); This variant is associated with the following publications: (PMID: 28771251, 28662915)
Invitae	RCV000412283	SCV001395546	pathogenic	Salla disease	2023-05-08	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 6 of the SLC17A5 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 SLC17A5 are known to be pathogenic (PMID: 10581036, 10947946, 15172001). For these reasons, this variant has been classified as 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: 371127). Disruption of this splice site has been observed in individual(s) with Salla disease (PMID: 28662915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.007%).
Genome-Nilou Lab	RCV000412283	SCV002027574	pathogenic	Salla disease	2021-09-05	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000437560	SCV003821030	pathogenic	not provided	2022-06-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000412283	SCV004201221	pathogenic	Salla disease	2023-08-13	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000412283	SCV002076730	pathogenic	Salla disease	2020-11-10	no assertion criteria provided	clinical testing
MyeliNeuroGene Lab, McGill University Health Center Research Institute	RCV002509063	SCV002540767	pathogenic	Intermediate severe Salla disease		no assertion criteria provided	clinical testing	The c.819+1G>A variant in SLC17A5 has previously been reported in an individual with Intermediate-severe Salla disease (Barmherzig et al. 2017).