ClinVar Miner

Submissions for variant NM_014251.3(SLC25A13):c.1638_1660dup (p.Ala554fs)

gnomAD frequency: 0.00001  dbSNP: rs80338725
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726889 SCV000703906 pathogenic not provided 2016-11-18 criteria provided, single submitter clinical testing
Invitae RCV000822371 SCV000963171 pathogenic Citrin deficiency 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala554Glyfs*17) in the SLC25A13 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 10369257, 14680984, 27405544). This variant is present in population databases (rs80338725, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with SLC25A13-related conditions (PMID: 27405544). ClinVar contains an entry for this variant (Variation ID: 6003). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001004526 SCV001163572 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000726889 SCV002020659 pathogenic not provided 2021-05-10 criteria provided, single submitter clinical testing
Genesolutions, Medical Genetics Institutes, Ho Chi Minh City, Vietnam RCV001004526 SCV002546529 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency 2022-06-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000006371 SCV003845174 pathogenic Citrullinemia type II 2023-02-24 criteria provided, single submitter clinical testing Variant summary: SLC25A13 c.1638_1660dup23 (p.Ala554GlyfsX17) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.1799dup [p.Tyr600Ter], c.1813C>T [p.Arg605Ter]). The variant allele was found at a frequency of 8.8e-05 in 251412 control chromosomes (gnomAD), predominantly at a frequency of 0.0012 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in SLC25A13 causing Citrullinemia Type II (8.8e-05 vs 0.0012), allowing no conclusion about variant significance. c.1638_1660dup23 has been reported in the literature as a biallelic genotype in multiple individuals affected with Citrullinemia (e.g. Song_2011, Wang_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: all four classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV002259302 SCV004203613 pathogenic Citrullinemia, type II, adult-onset 2024-03-28 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000726889 SCV004226563 pathogenic not provided 2022-08-11 criteria provided, single submitter clinical testing PM2, PM3_strong, PVS1
OMIM RCV000006371 SCV000026553 pathogenic Citrullinemia type II 1999-06-01 no assertion criteria provided literature only
GeneReviews RCV002259302 SCV000041254 not provided Citrullinemia, type II, adult-onset no assertion provided literature only
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital RCV001004526 SCV004800859 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency no assertion criteria provided clinical testing PVS1+PM3_VS+PP4

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