Provided a list of single base substitution and its coordinate, is there a tool to determine amino acid change?

Question

[Boboboe]

So I have a tab delimited file with this column structure

Chromosome | location on chromosome | original base | altered base | if the location is in the gene, Ensembl ID of the gene

Each line is a mutation

I would like to know for each of the mutation, if there are base substitution or the mutation doesn’t change the base. Is there a tool to do so?

Thanks!

Answer 1

[Kevin Blighe]

I presume that you mean that you want to determine if your variants / mutations will result in a change in an amino acid residue in the translated mRNA? - i.e., you are looking to determine which are missense / non-synonymous variants?

You are off to a good start with your input data. ANNOVAR can quickly determine this for you.

At minimal, your input data should be like this:

cut -f1-5 /Programs/annovar/myanno.avinput
16  50745926    50745926    C   T
20  14370   14370   G   A
20  17330   17330   T   A
20  1110696 1110696 A   G
20  1110696 1110696 A   T
20  1230237 1230237 T   G
20  1230288 1230288 T   0
20  1234568 1234570 TCT -
20  1234569 1234568 -   A

Then, we can annotate with a command like this:

/Programs/annovar/table_annovar.pl /Programs/annovar/myanno.avinput \
  /Programs/annovar/humandb/ \
  -buildver hg19 \
  -out test \
  -remove \
  -protocol refGene,cytoBand -operation g,r \
  -nastring \
  .

Check results:

cat test.hg19_multianno.txt

Chr Start   End Ref Alt Func.refGene    Gene.refGene    GeneDetail.refGene  ExonicFunc.refGene  AAChange.refGene    cytoBand
16  50745926    50745926    C   T   exonic  NOD2    .   nonsynonymous SNV   NOD2:NM_001293557:exon3:c.C2023T:p.R675W,NOD2:NM_022162:exon4:c.C2104T:p.R702W  16q12.1
20  14370   14370   G   A   intergenic  NONE,DEFB125    dist=NONE;dist=53943    .   .   20p13
20  17330   17330   T   A   intergenic  NONE,DEFB125    dist=NONE;dist=50983    .   .   20p13
20  1110696 1110696 A   G   intronic    PSMF1   .   .   .   20p13
20  1110696 1110696 A   T   intronic    PSMF1   .   .   .   20p13
20  1230237 1230237 T   G   intronic    RAD21L1 .   .   .   20p13
20  1230288 1230288 T   0   intronic    RAD21L1 .   .   .   20p13
20  1234568 1234570 TCT -   intronic    RAD21L1 .   .   .   20p13
20  1234569 1234568 -   A   .   .   .   .   .   .

If any variant / mutation will result in an amino acid change, then it will be listed as nonsynonymous under the ExonicFunc.refGene column.

ANNOVAR can do a lot of other stuff, and there is a quick set-up guide on the website.

Another option for you is Variant Effect Predictor.

Kevin