Hello everyone,
I found an exonic SNP (rs35124509) significantly associated with my phenotype. In order to characterize it, I used 3 type of score: The CADD: Combined Annotation Dependent Depletion score The SIFT: sorting intolerant from tolerant the Polyphen-2: polymorphism phenotyping v2
This variant is predicted as Polyphen = benign, SIFT = tolerated and CADD = 22.3. It seem a bit contradictory ? the CADD score predict it as being deleteriouse however, both SIFT and polyphen as tolerated/benign.
Moreover, I couldn't properly interpret the Genomic Evolutionary Rate Profiling (GERP) score. It is estimated for this genomic position as neutral (3.84).
What does it mean ? What do you think ?
Thank you for your help,
Y.
1 answer
The best you can do is use a consensus predictor like PredictSNP and see what each individual tool says. These tools have a ton of false positives - they can state that a change affects a protein more than it actually does in reality. You can trust their "benign" predictions, but take their "pathogenic" predictions with a grain of salt. If a multitude of tools say that a change is pathogenic, it is worth investigating.
W -> R does sound like a significant change, but the impact prediction depends on many different factors in addition to just the nature of the AA change.
Well, that was a good idea to use PredictSNP as a consensus but unfortunatly, the prediction is "neutral" ==> https://loschmidt.chemi.muni.cz/predictsnp2/?action=results&jid=8tnasd&gchr=
Try PredictSNP, not PredictSNP2: https://loschmidt.chemi.muni.cz/predictsnp1/ and pay attention to individual results, not just PredictSNP's consensus prediction.
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