Variant Prediction scores

Reference genome hg38: chr2-27243444-G-A

Reference genome hg19: chr2-27466312-G-A
CAD:Ala2202Thr
ACMG recommendation
Genet Med. 2015 May ; 17(5): 405–424.
• The use of multiple software programs for sequence variant
interpretation is recommended because the different programs each
have their own strengths and weaknesses depending on the
algorithm and in many cases performance can vary by the gene and
protein sequence.
General
MutationTaster
• An in silico prediction tool for the pathogenicity of a variant based on
evolutionary conservation, splice-site, mRNA, protein and regulatory
features.
• The disease potential is predicted by a naive Bayes classifier which
can be either 'disease causing' or 'polymorphism'.
• Prediction: Disease causing
Functional Analysis through Hidden Markov
Models (FATHMM)
• Predicts the effects of protein missense mutations
• Based on a combination of sequence conservation and 'pathogenicity
weights' which are derived from the relative frequencies of disease-
associated and functionally neutral amino acids mapping onto
conserved protein domains.
• Range -16.13 to +10.64
• Score: -5.29; Prediction: Damaging
Conservation
Genomic Evolutionary Rate Profiling (GERP)
• It is a conservation score calculated by quantifying substitution
deficits across multiple alignments of orthologues using the genomes
of 35 mammals.
• It ranges from -12.3 to 6.17, with 6.17 being the most conserved.
• Neutral Rate score (NR): 5.13; Rejected substitutions Score(RS): 5.13
Mutation assessor
• Predicts the functional impact of variation in proteins through
sequence conservation of protein homologs.
• Range -5.135 to +6.49
• Score: 3.1649 ; Prediction: Medium
Functional
SIFT (Sorts Intolerant From Tolerant)
• Tool for nonsynonymous variants based on sequence homology
derived from closely related sequences collected through PSI-BLAST.
• Range 0 to 1 with values less than 0.05 usually considered intolerant.
• Score: 0.005 ; Prediction: Damaging
 PROVEAN (Protein Variation Effect Analyzer)
• Predicts how nonsynonymous, MNP, or in-frame indel variant will
affect a protein's biological function. The prediction is based on
alignment-based scores derived from pairwise sequence alignments
between the query sequence and each of the related sequences at
the protein level. Range -14 to +14.
• Score :-2.71, -2.74 ; Prediction: Damaging