Submissions for variant NM_003491.4(NAA10):c.235C>T (p.Arg79Cys)

dbSNP: rs1057524031

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000436076	SCV000534361	uncertain significance	not specified	2016-12-23	criteria provided, single submitter	clinical testing	The R79C variant in the NAA10 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R79C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R79C as a variant of uncertain significance.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV000851511	SCV000994566	likely pathogenic	Intellectual disability	2018-04-10	criteria provided, single submitter	clinical testing
Invitae	RCV001305870	SCV001495218	uncertain significance	not provided	2020-10-14	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NAA10-related conditions. ClinVar contains an entry for this variant (Variation ID: 391316). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 79 of the NAA10 protein (p.Arg79Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.
Arnesen Lab, University of Bergen	RCV001730682	SCV001980711	pathogenic	Ogden syndrome		criteria provided, single submitter	clinical testing	The NAA10 c.235C>T p.(R79C) was identified in three related males with intellectual disability. The amino acid R79 is highly conserved and the R79C substitution introduce large physicochemical differences affecting the conserved acetyltransferase domain of NAA10. This variant is not present in population databases (gnomAD). Our functional studies showed that the N-terminal acetyltransferase activity of the The NAA10 c.235C>T p.(R79C) variant was decreased. We interpret p.(R79C) as a pathogenic variant based on in silico predictions, experimental evidence and a family history indicating X-linked inherited disease.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV001730682	SCV002102945	likely pathogenic	Ogden syndrome	2021-04-09	criteria provided, single submitter	clinical testing
OMIM	RCV001730682	SCV002570114	pathogenic	Ogden syndrome	2022-09-08	no assertion criteria provided	literature only