Submission Details

Variants in NAA10 were first reported in relation to X-linked NAA10-related syndrome as early as 2011 (Rope et al., PMID: 21700266). NAA10-related syndrome is characterized by substantial phenotypic variability, ranging from a severe lethal phenotype in males originally described as Ogden syndrome, to milder forms of intellectual disability in both males and females (PMID: 30054457). Additional findings in some individuals may include growth failure, dysmorphic facial features, hypotonia and/or hypertonia, and cardiac and skeletal abnormalities. Syndromic microphthalmia (Lenz microphthalmia syndrome) has been reported in males with NAA10 variants resulting in decreased mRNA (splice, frameshift and polyadenylation signal variants) (PMID: 30842225). Numerous unique variants in NAA10, mostly missense, have been reported, with some variants occurring de novo. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 22 probands in 6 publications (PMIDs: 21700266, 24431331, 25099252, 26522270, 31127942, 35039925). More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.

NAA10 encodes the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. This gene-disease association is supported by protein interaction with NAA15, also involved in syndromic intellectual disability; functional alteration in non-patient cells; and phenotype characterization of a zebrafish model (1.5 points).

In summary, there is definitive evidence supporting the relationship between NAA10 and X-linked NAA10-related syndrome. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on September 2nd 2020 (SOP Version 7). As of January 10th, 2023, this record underwent administrative updates to include minor edits to the evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added, and the classfication remains the same.

NAA10 was first reported in relation to X-linked NAA10-related syndrome in 2011 (Rope et al., PMID: 21700266). NAA10-related syndrome is characterized by substantial phenotypic variability, ranging from a severe lethal phenotype in males originally described as Ogden syndrome, to milder forms of intellectual disability in both males and females (PMID: 30054457). Additional findings in some individuals may include growth failure, dysmorphic facial features, hypotonia and/or hypertonia, and cardiac and skeletal abnormalities. Syndromic microphthalmia (Lenz microphthalmia syndrome) has been reported in males with NAA10 variants resulting in decreased mRNA (splice, frameshift and polyadenylation signal variants) (PMID: 30842225).

Numerous unique variants in NAA10, mostly missense, have been reported, with some variants occurring de novo. Variants in this gene have been reported in at least 22 probands in 6 publications (PMIDs: 21700266, 24431331, 25099252, 26522270, 31127942, 35039925). More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.

NAA10 encodes the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. This gene-disease relationship is also supported by protein interaction with NAA15, also involved in syndromic intellectual disability; functional alteration in non-patient cells; and a zebrafish model.

In summary, there is definitive evidence supporting the relationship between NAA10 and X-linked NAA10-related syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on September 2, 2020 (SOP Version 7). As of January 10, 2023, this record underwent administrative updates to include minor edits to the evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added, and the classification remains the same.