Submissions for variant NM_002547.3(OPHN1):c.164C>T (p.Ser55Phe)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004785102	SCV005397587	likely pathogenic	X-linked intellectual disability-cerebellar hypoplasia syndrome	2024-02-05	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (C>T) at position 164 of the coding sequence of the OPHN1 gene that results in a serine to phenylalanine amino acid change at residue 55 of the oligophrenin 1 protein. This residue falls in the BAR domain of the protein (Uniprot). This de novo variant was not transmitted from either parent. This variant is absent from ClinVar but is present in the gnomAD v4.0.0 population database (2 of 1,049,075 alleles, 0.0002%). This variant has not been observed in an individual affected by a OPHN1-related disorder in the published literature, to our knowledge. Multiple bioinformatic tools predict that this amino acid change would be neutral, and the Ser55 residue at this position is moderately conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: BP4, PM2, PS2