Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001839269 | SCV002099246 | uncertain significance | Clark-Baraitser syndrome | 2021-07-02 | criteria provided, single submitter | clinical testing | The de novo c.3206+408T>G variant identified in the TRIP12 gene is a deep intronic variant within intron 21/41 of transcript NM_001348323.1. TRIP12 is alternatively spliced, and this variant may have different nomenclature and fall within a different intron in an alternative transcript, although it is intronic in all currently annotated transcripts. This variant is absent in gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithm SpliceAI does not predict an alteration to splicing (delta score:0.00), and the Transcript inferred Pathogenicity (TraP) score is 0.112 (75-90% score-percentile), which is not strongly indicative of a damaging effect. This variant is absent from ClinVar and to our current knowledge has not been reported inaffected individuals in the literature. While it is found de novo in the affected individual and absent from population databases, the lack of additional compelling evidence for its pathogenicity results in its classification here as a Variant of Uncertain Significance. |