Protein sequence from patient data Currently, I am working on NGS data and my aim is to get significance prediction of variants present in the vcf file. As we know about SIFT Score for significance score prediction, I am trying to understand how this score works. When I read its reference paper, in the method section, the procedure to determine the sift score starts with patient protein query sequence. 

My question is how to get patient protein sequence from patient data (either vcf file or bam file) (which is not explained in the paper). Rest I can follow by other algorithms like PSI-BLAST &amp; MOTIF.

Any suggestions....

Thanks
Ensembl now have a tool called Haplosaurus (still in beta) which will convert your phased VCF into actual protein sequences. 


  Haplosaurus
  
  haplo is a local tool implementation of the same functionality that
  powers the Ensembl transcript haplotypes view. It takes phased
  genotypes from a VCF and constructs a pair of haplotype sequences for
  each overlapped transcript; these sequences are also translated into
  predicted protein haplotype sequences. Each variant haplotype sequence
  is aligned and compared to the reference, and an HGVS-like name is
  constructed representing its differences to the reference.
  
  This approach offers an advantage over VEP's analysis, which treats
  each input variant independently. By considering the combined change
  contributed by all the variant alleles across a transcript, the
  compound effects the variants may have are correctly accounted for.
  
  haplo shares much of the same command line functionality with vep, and
  can use VEP caches, Ensembl databases, GFF and GTF files as sources of
  transcript data; all vep command line flags relating to this
  functionality work the same with haplo.
  
  Usage
  
  Input data must be a VCF containing phased genotype data for at
  least one individual; no other formats are currently supported.
  
  When using a VEP cache as the source of transcript annotation, the
  first time you run haplo with a particular cache it will spend some
  time scanning transcript locations in the cache.

./haplo -i input.vcf -o out.txt -cache