**Question:** Base substitution of GAC (Asp) to GAG (Glu) is an example of:

A. Point mutation
B. Frameshift mutation
C. Nonsense mutation
D. Missense mutation

**Correct Answer:** D. Missense mutation

**Core Concept:**
In molecular biology, a point mutation refers to a change in a single nucleotide base in an organism's DNA or RNA sequence. This change can alter the amino acid sequence of the protein translated from that genetic sequence. There are four types of point mutations:

1. **Nonsense mutations:** These occur when a premature stop codon (UAA, UAG, or UGA) is introduced, leading to a truncated protein due to the early termination of translation.
2. **Frame-shifting mutations:** These occur when a single base change causes a shift in the reading frame of the mRNA, which leads to a completely different protein sequence.
3. **Silent mutations:** These involve a change in the base but do not affect the amino acid sequence, as the mutated codon codes for the same amino acid as the wild-type codon.
4. **Missense mutations:** These involve a change in the base that results in a different amino acid being incorporated into the protein sequence. This can lead to a change in protein function or structure, potentially causing a disease phenotype.

**Why the Correct Answer is Right:**
A missense mutation occurs when a single nucleotide base change leads to a change in the amino acid encoded by the mutated codon. In this case, the substitution from GAC (Asp) to GAG (Glu) is a missense mutation. The change from aspartate (Asp) to glutamate (Glu) results in an alteration of the protein's amino acid sequence, potentially affecting protein function or structure.

**Why Each Wrong Option is Incorrect:**
A. **Nonsense mutations (Option A):** These introduce a premature stop codon, leading to a truncated protein due to early termination of translation. The substitution of GAC to GAG does not fit this category as it changes the amino acid sequence.

B. **Frame-shifting mutations (Option B):** These cause a shift in the reading frame, leading to a completely different amino acid sequence. The substitution of GAC to GAG does not fit this category as it changes the same amino acid.

C. **Silent mutations (Option C):** These change the base but do not alter the amino acid sequence. The substitution of GAC to GAG changes the amino acid (Asp to Glu), making this a missense mutation rather than a silent mutation.

D. **Missense mutations (Correct answer):** This is the correct category for the given substitution, as it leads to a change in the amino acid sequence. In this case, the substitution of GAC to GAG results in an alteration of the encoded amino acid (Asp to Glu).

**Clinical Pearl (High-yield information):**
Missense mutations are a significant category of genetic variations, as they can lead to a range of clinical manifestations, including:

1. **Alteration of protein function:** Changes