A point mutation in which one base pair in the DNA sequence is replaced by another. In transition mutations a pyrimidine base (i.e. thymine or cytosine) is replaced by another pyrimidine base or a purine base (adenine or guanine) is replaced by another purine base; whereas in transversion mutations a pyrimidine base is replaced by a purine base, or vice versa. A substitution thus alters the base sequence of the genetic code; however, the effect on the gene product depends on the nature of the change. A synonymous substitution changes the codon to another that codes for the same amino acid, whereas a nonsynonymous substitution creates a codon for a different amino acid, which may or may not affect the functioning of the protein. Sickle-cell anaemia is an example of a substitution mutation in which thymine is replaced by adenine in the triplet coding for the sixth amino acid in the β‎-chain of haemoglobin.