Hello all,

I'm struggling in understanding the HGVS 3'rule, which states:

3'rule: for all descriptions, the most 3' position possible of the reference sequence is arbitrarily assigned to have been changed.

• the 3'rule also applies for changes in single residue stretches and tandem repeats (nucleotide or amino acid).
• the 3'rule applies to ALL descriptions (genome, gene, transcript, and protein) of a given variant.
• exception: deletions/duplications around exon/exon junctions using c., r. or n. reference sequences (see Numbering).

Also, from Mitomap, the rule can also be written like this:

For deletions, duplications and insertions the most 3' position possible is arbitrarily assigned to have been changed. This rule also applies to variants in single residue stretches (mono-nucleotide or amino acid) or tandem repeats."

To give an example, my variant caller gives a variant on the chrM : m.57T>TC, but according to the 3'rule it should be named m.60T>TC (if I understood correctly). But I fail to understand why the rule exists in the beginning, because to me these are two different variants: considering the reference sequence (NC_012920) they won't give the same variant sequence (TATCTTTCG vs TATTTTCCG).

Do you have any clear explanation and/or examples to understand why?