Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000624650 | SCV000741088 | likely pathogenic | Inborn genetic diseases | 2020-02-19 | criteria provided, single submitter | clinical testing | The alteration results in an in-frame deletion: The c.992_1006del15 (p.Q331_K335del) alteration, located in coding exon 1 of the POU3F3 gene, results from an in-frame deletion of 15 nucleotides at positions 992 to 1006. This results in the deletion of 5 amino acids between codons 331 and 335. The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the POU3F3 c.992_1006del15 alteration was not observed, with coverage at this position. The alteration has been observed in affected individuals: This alteration was confirmed de novo in a 12 year old female patient with borderline ID, delayed speech and motor development, and dysmorphic features including cupped ears, long/narrow face, full lips, and high/narrow palate (Snijders Blok, 2019). The deleted amino acids are conserved throughout evolution: The Q331_K335 amino acids are completely conserved in available vertebrate species. The alteration is predicted deleterious by in silico modeling: The p.Q331_K335del alteration is predicted to be deleterious with a score of -38.00 by PROVEAN in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |