ClinGen Dosage Sensitivity Curation Page

PHF3

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
25363768 Iossifov et al (2014) used exome sequencing (including parental samples and confirmatory methods for de novo variants) on Simons Simplex Collection samples to identify variants associated with autism spectrum disorder. One de novo frameshift variant was identified in a patient. Of note, this appears to be the same patient described by Dong et al (2014, PMID 25284784).
28263302 Yuen et al (2017) performed genome sequencing (including parental samples and confirmatory methods for de novo variants) on families with autism spectrum disorder. One de novo frameshift variant was identified in a patient (the DNA sequence change occurred in exon 10 of 15 or 12 of 17, depending on transcript). In this cohort, the following PHF3 putative loss-of-function variants were also identified: a frameshift of unknown inheritance, a frameshift inherited from an unaffected parent (sequence change located upstream of the previously mentioned de novo change), and a nonsense variant in the last exon inherited from an unaffected parent.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.