The association between ZNF41 and X-linked non-syndromic intellectual disability was first suggested in 2013 (Shoichet et al., PMID: 14628291). This study reported three unrelated families with intellectual disability and variants involving ZNF41. One female was found to have a de novo balanced X;7 translocation disrupting ZNF41. This translocation was not counted as evidence because the impact of the breakpoints on neighboring genes cannot be ruled out. The second family had two affected brothers with a maternally inherited missense variant in ZNF41. The third family included an affected male proband and an affected sister with borderline ID with a maternally inherited deep intronic variant in ZNF41 that resulted in loss of specific ZNF41 splice variants. The two ZNF41 sequence variants were found to have high population frequencies in gnomAD (v2.1.1) and were not scored as evidence. No additional studies have been reported since then with causative ZNF41 variants in affected individuals. In summary, there is no valid genetic evidence to support an association between ZNF41 and X-linked nonsyndromic intellectual disability, so this gene-disease association is disputed. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 09/02/2020 (SOP Version 7).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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