ClinVar Miner

Submissions for variant NM_003491.4(NAA10):c.346C>T (p.Arg116Trp)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000128609 SCV000154971 pathogenic Ogden syndrome 2016-03-31 criteria provided, single submitter clinical testing
GeneDx RCV000413890 SCV000491192 pathogenic not provided 2021-11-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; a reduction in the catalytic activity (Popp et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25099252, 23871722, 23020937, 27296530, 27094817, 29957440, 30577886)
Institute of Human Genetics, University of Leipzig Medical Center RCV000128609 SCV001429211 pathogenic Ogden syndrome 2019-08-08 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000413890 SCV001500676 pathogenic not provided 2021-01-01 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000128609 SCV003807764 likely pathogenic Ogden syndrome 2022-10-29 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PM6 moderated
3billion RCV000128609 SCV003841901 pathogenic Ogden syndrome 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.96). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000139644). The variant has been previously reported as de novo in a similarly affected individual (PMID: 27094817). A different missense change at the same codon (p.Arg116Gln) has been reported to be associated with NAA10 related disorder (ClinVar ID: VCV001326724). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV004528848 SCV004046291 pathogenic NAA10-related disorder criteria provided, single submitter clinical testing This variant has been previously reported as a de novo change in several individuals with NAA10-related disorder (PMID: 25099252, 29957440). In vitro studies using N-terminal acetylation assays demonstrated protein with this variant had significant reduction in the catalytic activity of the enzyme in comparison to wild type protein (PMID: 25099252). The c.346C>T (p.Arg116Trp) variant is absent from the gnomAD population database and thus is presumed to be rare. The c.346C>T (p.Arg116Trp) variant affects a highly conserved amino acid; however, in silico tools used to predict the effect of this variant on protein function yield discordant results. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.346C>T (p.Arg116Trp) variant is classified as a Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004528848 SCV004108891 pathogenic NAA10-related disorder 2023-10-04 criteria provided, single submitter clinical testing The NAA10 c.346C>T variant is predicted to result in the amino acid substitution p.Arg116Trp. This variant has been reported in the heterozygous and hemizygous states in patients with intellectual disability, development delay and eyelid myoclonus; in the majority of cases, this variant was found to be de novo (see for example, Rauch et al. 2012. PubMed ID: 23020937; Valentine et al. 2018. PubMed ID: 29957440; Baker et al. 2019. PubMed ID: 30577886). This variant was also confirmed to be de novo in an individual with intellectual disability and microcephaly tested at PreventionGenetics. This variant has not been reported in a large population database (, indicating it is rare in the general population. This variant is interpreted as pathogenic.
OMIM RCV000128609 SCV000257346 pathogenic Ogden syndrome 2015-05-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000128609 SCV000734762 pathogenic Ogden syndrome no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000413890 SCV001929008 likely pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000413890 SCV001956497 pathogenic not provided no assertion criteria provided clinical testing
Laboratory of Medical Genetics, University of Torino RCV000128609 SCV002583290 pathogenic Ogden syndrome 2022-10-09 no assertion criteria provided research

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