functional assessment of synonymous SNPs

Question

[12021560-002]

Hi I have a question. I have a gene list and variants associated with these genes and want to carry out the functional assessment of those variants although I have found some tools for nonsynonymous variants like SIFT,POLYPHEN etc. but I have not found any tool for functional assessment of synonymous variants. Could you please suggest name of some tools for synonymous variants which help me to get functional insight of these variants based on certain parameters like a threshold or score???

Answer 1

[Denise CS]

Use the Variant Effect Predictor and select the LoFtool, available both in the online interface and Perl script as a VEP plugin. LoFtool gives you 'a rank of genic intolerance and consequent susceptibility to disease based on the ratio of Loss-of-function (LoF) to synonymous mutations for each gene in 60,706 individuals from ExAC).

Answer 2

[Ram]

Synonymous variants are not significant at the protein level - you should look at DNA/RNA level effects. Look for motifs affected, binding sites disrupted, cryptic splice sites created, etc.

Tools should not the first thing on your list - the concept of consequence/effect should. Your biological question will drive the kind of effects relevant to your analysis, and the kind of effect you're looking for will determine what tool would be appropriate.

[Denise CS]

The VEP also tells whether the variant falls in a regulatory motif or not. Use the --regulatory flag with the script version, or check if the 'Get the regulatory region consequence' is selected under Extra options in the online version.

[Ram]

I did not know of this option in VEP - thank you so much!

[John]

Tools should not the first thing on your list - the concept of consequence/effect should.

Truth!

Answer 3

[Garan]

You could also try something like SilVA

http://compbio.cs.toronto.edu/silva/

Identification of deleterious synonymous variants in human genomes.