Submissions for variant NM_138386.3(NAF1):c.227C>G (p.Ala76Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004785196	SCV005397820	uncertain significance	Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7	2024-04-26	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (C>G) at position 227 of the coding sequence of the NAF1 gene that results in an alanine to glycine amino acid change at residue 76 of the nuclear assembly factor 1 ribonucleoprotein protein. This variant is absent from ClinVar and has not been observed in individuals affected by a NAF1-related disorder in the published literature, to our knowledge. This variant is present in 1 of 612858 alleles (0.00016%) in the gnomAD v4.0.0 population dataset. Multiple bioinformatic tools predict that this amino acid change would be neutral, and the Ala76 residue at this position is poorly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP4, PM2