Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.

ABSTRACT:

Background

TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

Methods

We conducted splicing analyses using a minigene construct containing TP53 exons 2 to 9 transfected into human breast cancer SKBR3 cells, and compared results against different splice prediction methods, including

SUBMITTER: Fortuno C 

PROVIDER: S-EPMC11715486 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature