ABSTRACT PNMT is a protein-coding gene that codes for the Phenylethanolamine N-methyltransferase enzyme. It is primarily associated with neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. In the present study, over 17 different sequence-based and structure-based tools as well as 4 MSA tools and a ConSurf server were used to screen the highly deleterious single nucleotide polymorphisms (SNPs) of PNMT. Out of 286 missense SNPs, five were found to be deleterious (Y35D, I78N, I78S, G79D and L217Q) after the screening process. This was followed by performing oncogenic and phenotypic analysis, modelling of mutant proteins, structural analysis, STRING analysis, and post-translational modification (PTM) analysis. Finally, molecular dynamics simulations analysis was performed in duplicates to understand the impact of deleterious mutations on the stability of PNMT. All five mutations were predicted to be oncogenic and PTM analysis revealed that mutation Y35D occurs at a tyrosine kinase phosphorylation site.