ClinVar Miner

Submissions for variant NM_015665.6(AAAS):c.1432C>T (p.Arg478Ter)

gnomAD frequency: 0.00007  dbSNP: rs121918548
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255523 SCV000321310 pathogenic not provided 2020-11-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect due to mislocalization of the ALADIN protein (Krumbholtz et al., 2006); Nonsense variant predicted to result in protein truncation, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 11062474, 12008750, 16609705, 11914417, 14646395, 20499090, 30381913, 29874194, 31980526)
Pathology and Clinical Laboratory Medicine, King Fahad Medical City RCV000005343 SCV000996292 pathogenic Glucocorticoid deficiency with achalasia criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000255523 SCV001249015 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV001778647 SCV002016318 pathogenic Neurodevelopmental disorder 2021-10-07 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000005343 SCV002019721 pathogenic Glucocorticoid deficiency with achalasia 2020-08-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000005343 SCV002799259 pathogenic Glucocorticoid deficiency with achalasia 2022-05-12 criteria provided, single submitter clinical testing
Invitae RCV000255523 SCV004294182 pathogenic not provided 2023-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg478*) in the AAAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the AAAS protein. This variant is present in population databases (rs121918548, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with triple A syndrome (PMID: 11062474, 14646395, 29874194, 30381913). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5040). 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.
OMIM RCV000005343 SCV000025521 pathogenic Glucocorticoid deficiency with achalasia 2002-03-26 no assertion criteria provided literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000005343 SCV001132828 pathogenic Glucocorticoid deficiency with achalasia 2019-01-29 no assertion criteria provided clinical testing

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