ClinVar Miner

Submissions for variant NM_014251.3(SLC25A13):c.1177+1G>A

gnomAD frequency: 0.00001  dbSNP: rs80338722
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000006369 SCV000470725 pathogenic Citrullinemia type II 2017-04-27 criteria provided, single submitter clinical testing The SLC25A13 c.1177+1G>A variant, which occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product, is a common pathogenic variant in Japanese individuals with citrin deficiency (Kobayashi et al. 2005). Across a selection of available literature, the c.1177+1G>A variant has been identified in a homozygous state in 11 patients and in a compound heterozygous state in at least three patients (Kobayashi et al. 1999; Ohura et al. 2001; Tamamori et al. 2002; Liu et al. 2014). The c.1177+1G>A variant was absent from 234 controls and is reported at a frequency of 0.01923 in the Japanese in Tokyo, Japan population of the 1000 Genomes Project. Based on the evidence from the literature and the potential impact of splice donor variants, the c.1177+1G>A variant is classified as pathogenic for citrin deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000808307 SCV000948411 pathogenic Citrin deficiency 2024-01-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the SLC25A13 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs80338722, gnomAD 0.07%). Disruption of this splice site has been observed in individuals with citrin deficiency (PMID: 10369257, 12424587, 12512993, 22710133, 23430852). This variant is also known as IVS11+1G>A. ClinVar contains an entry for this variant (Variation ID: 6002). Studies have shown that disruption of this splice site results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 22710133). For these reasons, this variant has been classified as Pathogenic.
Genesolutions, Medical Genetics Institutes, Ho Chi Minh City, Vietnam RCV000006370 SCV002546528 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency 2022-06-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV002259301 SCV004209358 pathogenic Citrullinemia, type II, adult-onset 2024-02-13 criteria provided, single submitter clinical testing
OMIM RCV000006369 SCV000026551 pathogenic Citrullinemia type II 2001-05-01 no assertion criteria provided literature only
OMIM RCV000006370 SCV000026552 pathogenic Neonatal intrahepatic cholestasis due to citrin deficiency 2001-05-01 no assertion criteria provided literature only
GeneReviews RCV002259301 SCV000041250 not provided Citrullinemia, type II, adult-onset no assertion provided literature only
Natera, Inc. RCV001277073 SCV001463808 pathogenic Late-onset citrullinemia 2020-09-16 no assertion criteria provided clinical testing

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