Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001371623.1(TCOF1):c.2765C>G(p.Ser922Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S922L) has been classified as Benign.
TCOF1 (HGNC:11654): (treacle ribosome biogenesis factor 1) This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.2603516).
.;Loss of phosphorylation at S922 (P = 0.0087);.;.;Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);Loss of phosphorylation at S922 (P = 0.0087);