I'm using annovar (which sometimes uses dbNSFP) for annotating variants against different databases, such as: SIFT, Polyphen2, Mutation Taster and etc
Let's say we identified a mutation already associated with a disease on the position: chr3:52183866 G A -> genotype 1/1 == AA
This NONSENSE variant was annotated by Annovar and predicted to have SIFT Score of 1.0 and Polyphen2 Score of 0.735458
grep "52183866" hg19_avsift.txt: 3 52183866 52183866 G A 1 R *
grep "52183866" hg19_ljb_pp2.txt: 3 52183866 52183866 G A 0.735458 NA
1) Why I can find this scores for nonsense mutations on the database files provided by annovar if I cannot search for nonsense mutations direct on the websites of SIFT and Polyphen2 ? How this was calculated ?
2) What is the difference between a nonsense variant that has Sift score of 0 and 1.0 ?
3 52183866 52183866 G A 1 R *
1 10720360 10720360 T A 0 K *
3) Is there any algorithm I could use for Variant prioritization of nonsense variants ? I'm considering removing all SIFT and Polyphen2 Scores of nonsense variants from our internal database. So that when we filter our list of variants using the rule let's say "Sift <= 0.05" we don't exclude nonsense variants that have a sift score >= 0.05. I would like some suggestions for this problem.
Btw, I read this post Stop-gain mutation predicted as benign by SIFT/Polyphen2? before posting :) so I know I should not trust sift scores for nonsense variants. I also know sift scores are calculated for all the positions of the genome. I'm just trying to understand what's happening on this problem.
Thank you for reading! Best Regards.