ClinVar Miner

Submissions for variant NM_012434.5(SLC17A5):c.1259+1G>A

gnomAD frequency: 0.00001  dbSNP: rs146095590
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409414 SCV000485703 likely pathogenic Salla disease 2016-02-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000409414 SCV001448469 likely pathogenic Salla disease 2020-11-23 criteria provided, single submitter clinical testing Variant summary: SLC17A5 c.1259+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251382 control chromosomes. c.1259+1G>A has been reported in the literature in individuals affected with Sialic Acid Storage Disorder (example, Kleta_2003, Froissart_2005). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000409414 SCV002242580 pathogenic Salla disease 2023-12-18 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the SLC17A5 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs146095590, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with free sialic acid storage disorders (PMID: 12794688, 15805149). This variant is also known as IVS9+1G>A. ClinVar contains an entry for this variant (Variation ID: 370393). Studies have shown that disruption of this splice site results in skipping of exon 9 and introduces a premature termination codon (PMID: 12794688). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV003137984 SCV003827952 pathogenic not provided 2022-03-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000409414 SCV004201222 pathogenic Salla disease 2023-08-07 criteria provided, single submitter clinical testing
OMIM RCV000005969 SCV000026151 pathogenic Sialic acid storage disease, severe infantile type 2003-07-01 no assertion criteria provided literature only

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