Past exam of the biochemistry and Molecular Biology course of the University of Cambridge / 2025 / Paper 2 / Section C / 14 / s

Replacing the acceptor's A with C changes the canonical $3^{\prime }$ splice site from AG to CG. The predicted primary effect is impaired recognition of the exon-5 acceptor, reducing normal exon-5 inclusion. If the processing machinery instead selects exon 6, TCF-long would decrease and TCF-short would increase, removing the long-specific corepressor-interaction sequence from more of the translated products. Other outcomes are possible, including a cryptic acceptor, intron retention, unstable transcripts or altered total expression; the nucleotide change does not uniquely determine one mature product. Test allele-specific RNA splicing by junction assays and sequencing, with matched alleles or an edited endogenous locus. Unlike a repeat indel, this is initially a splice-site perturbation rather than necessarily a coding-region frameshift mutation.