We are having a hard time to determine a "representative" amino acid change that resulted from a genomic point mutation. Obviously, a genomic point mutation in a coding region leads to a protein sequence change (including missense, nonsense, splice-variants... etc). Problem is, there are multiple possible transcripts (from a same gene) that are affected from the point mutation, and the result can be different for each transcript. For example, one mutation can be synonymous in transcript A, but missense in transcript B and nonsense in transcript C. Question is, if we need to pick one AA change, which transcript should we use?
I understand genomic mutation to AA change cannot be always 1 to 1. However in a usual biological paper, researchers tend to report only one AA acid change from one mutation. In my case, we are counting the ratio of missense, nonsense, synonymous... from a discovered mutation list, in which we need to assign one AA change type to one mutation.
My colleagues had the same opinion with yours. I had one question in how to measure the "severity" of the mutation. For instance, nonsense is likely to be more severe than missense mutations but nonsense at the end of the product (protein) may not be as severe as the one in the front side. As you suggested, using Ensembl VEP may be an option for it. And thank you for the table! it would be very helpful for us.