ClinVar Miner

Submissions for variant NM_012434.5(SLC17A5):c.533del (p.Thr178fs)

gnomAD frequency: 0.00006  dbSNP: rs727504156
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153956 SCV000203574 pathogenic not provided 2013-12-11 criteria provided, single submitter clinical testing
GeneDx RCV000153956 SCV000490802 pathogenic not provided 2019-08-07 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect in deficiency of lysosomal transport (Mancini et al., 1991); Frameshift variant predicted to result in protein truncation or nonsense mediated decay 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); This variant is associated with the following publications: (PMID: 2010546, 10947946, 12709150, 15805149, 10581036, 31589614)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588857 SCV000699340 pathogenic Salla disease 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The SLC17A5 c.533delC (p.Thr178Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent SLC17A5 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 8/118852 control chromosomes at a frequency of 0.0000673, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC17A5 variant (0.0023717). Multiple publications have cited the variant in compound heterozygote affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV000588857 SCV001163089 pathogenic Salla disease 2024-03-12 criteria provided, single submitter clinical testing
Invitae RCV000588857 SCV001232860 pathogenic Salla disease 2024-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr178Asnfs*34) in the SLC17A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC17A5 are known to be pathogenic (PMID: 10581036, 10947946, 15172001). This variant is present in population databases (rs727504156, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with sialic acid storage disorders (PMID: 10581036, 15805149). ClinVar contains an entry for this variant (Variation ID: 167693). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000153956 SCV001480119 pathogenic not provided 2021-02-01 criteria provided, single submitter clinical testing
Genomic Medicine Lab, University of California San Francisco RCV000588857 SCV001572959 pathogenic Salla disease 2020-06-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000153956 SCV002022593 likely pathogenic not provided 2021-06-24 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000588857 SCV002027577 pathogenic Salla disease 2021-09-05 criteria provided, single submitter clinical testing
OMIM RCV000005968 SCV000026150 pathogenic Sialic acid storage disease, severe infantile type 1999-12-01 no assertion criteria provided literature only
Counsyl RCV000588857 SCV001132286 likely pathogenic Salla disease 2017-09-22 no assertion criteria provided clinical testing
Natera, Inc. RCV000588857 SCV001453513 pathogenic Salla disease 2020-09-16 no assertion criteria provided clinical testing
Undiagnosed Diseases Network, NIH RCV000005968 SCV004812052 pathogenic Sialic acid storage disease, severe infantile type 2022-06-21 no assertion criteria provided clinical testing

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