Table 2 In silico prediction analysis of c.961 + 1G > A splice site variant effect on PEPCK-C function and structure
c.961 + 1G > A (p.His322Glufs81*) | ||
|---|---|---|
Exon | 6 | |
gnomAD and/or 1000G | rs776767788 (Total allele frequency = 0.00002459) | |
Mutation taster | Disease-causing (Leads to loss of function) | |
Splice site | Loss of the donor splice site at exon 6 / intron 5 | |
Effect | mRNA | Frameshift due to the retention of intron 5 and the generation of a premature stop codon at position 1209 |
Protein | Normal translation changes from residue 322 and prematurely terminates at 403 | |
Critical protein domains affected | Substrate binding 403–405 GTP binding sites at 405, 436, 533 Abolished acetylation sites at 473, 521, 524, and 594 | |
ACMG/AMP classification | Pathogenic (PVS1, PM2, and PP5) | |