SNP effect predictions (PKU)

Predictions of SNP effect

The three methods we used, agree on ARG158Gln, Arg243Gln, Leu255Ser and Arg408Trp to have damaging effect and agree on Met276Val to be functionally neutral. Glu76Gly and Ser87Arg are reported to be benign by SIFT and PolyPhen and damaging, but with low reliability, by SNAP.
For the other three SNPs, there is no agreement or clear tendency of the predictions.

SIFT

76 from E to G TOLERATED with a score of 0.18.
   Median sequence conservation: 3.01
   Sequences represented at this position:74

87 from S to R TOLERATED with a score of 0.54.
   Median sequence conservation: 2.99
   Sequences represented at this position:75

158 from R to Q AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 2.98
   Sequences represented at this position:76

172 from Q to H AFFECT PROTEIN FUNCTION with a score of 0.03.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

243 from R to Q AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

255 from L to S AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

276 from M to V TOLERATED with a score of 0.06.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

322 from A to G AFFECT PROTEIN FUNCTION with a score of 0.01.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

337 from G to V AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:77

408 from R to W AFFECT PROTEIN FUNCTION with a score of 0.00.
   Median sequence conservation: 3.01
   Sequences represented at this position:75

PolyPhen

We report here the results for PolyPhen(HumDiv) and PolyPhen(HumVar), but only consider HumVar as this is the training set recommended by PolyPhen for our task.

GLU76GLY

HumDiv
BENIGN 0.002 (sensitivity: 0.99; specificity: 0.30)
HumVar
BENIGN 0.007 (sensitivity: 0.97; specificity: 0.46)

SER87ARG

HumDiv
BENIGN 0.091 (sensitivity: 0.93; specificity: 0.85)

HumVar
BENIGN 0.094 (sensitivity: 0.91; specificity: 0.68)

R158Q

HumDiv
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

HumVar
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

Q172H

HumDiv
POSSIBLY DAMAGING 0.705 (sensitivity: 0.86; specificity: 0.92)

HumVar
BENIGN 0.170 (sensitivity: 0.89; specificity: 0.72)

R243Q

HumDiv
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

HumVar
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

L255S

HumDiv
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

HumVar
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

M276V

HumDiv
POSSIBLY DAMAGING 0.517 (sensitivity: 0.88; specificity: 0.90)

HumVar
BENIGN 0.081 (sensitivity: 0.92; specificity: 0.67)

A322G

HumDiv
POSSIBLY DAMAGING 0.895 (sensitivity: 0.82; specificity: 0.94)

HumVar
POSSIBLY DAMAGING 0.707 (sensitivity: 0.78; specificity: 0.85)

G337V

HumDiv
BENIGN 0.291 (sensitivity: 0.91; specificity: 0.89)

HumVar
POSSIBLY DAMAGING 0.597 (sensitivity: 0.81; specificity: 0.83)

R408W

HumDiv
PROBABLY DAMAGING 1.000 (sensitivity: 0.00; specificity: 1.00)

HumVar
PROBABLY DAMAGING 0.999 (sensitivity: 0.09; specificity: 0.99)

SNAPFUN

Including only predictions with:
 	RI >= 0 
	Expected Accuracy >= 50%

nsSNP	Prediction	Reliability Index	Expected Accuracy
-----	------------	-------------------	-------------------
E76G	Non-neutral		1			63%
S87R	Non-neutral		0			58%
R158Q	Non-neutral		5			87%
Q172H	 Neutral 		4			85%
R243Q	Non-neutral		2			70%
L255S	Non-neutral		1			63%
M276V	 Neutral 		1			60%
A322G	 Neutral 		1			60%
G337V	 Neutral 		1			60%
R408W	Non-neutral		3			78%