Can SIFT predict synonymous variants?

[yywyaoyaowu]

Hi,
I wonder if SIFT can predict synonymous deleterious? I found some novol mutation didn't affect the aa, but with SIFT score <0.05. I wonder how this happen? SIFT is an algorithm that predicts whether an amino acid substitution is deleterious to protein function.
Thanks very mich!

[pauline-ng]

This happens if the reference amino acid is predicted deleterious. This happens about 1% of the time. Sometimes it's an error in the reference genome.

[yywyaoyaowu]

SIFT can predict deleterious amino acids in reference genome. But they can not predict deleterious mutation caused by synonymous mutation. Right? Thanks very much!

[pauline-ng]

SIFT looks at the amino acid present in the protein and predicts if the amino acid present in the protein affects structure/function from an evolutionary perspective. It does not consider splicing or regulatory (what synonymous mutations can affect).

Again, synonymous means your "new" amino acid is the same as the reference amino acid, and there is a small % of time SIFT predicts this as deleterious. Sometimes this happens in pseudogenes or sequencing error. I suggest you look at the protein alignment and if you see other homologous proteins have another amino acid strongly conserved at that position, then the reference/native amino acid is affecting protein function.