[ensembl-dev] inconsistency when mapping the same variant from protein to genomics vs genomics to protein

[Andrew Parton]

Hi David,

I’ve taken a look at this issue this morning and I think I can see what’s going on. I can reproduce this issue with the query: perl vep -id 'TP53:p.E285V' --database --force_overwrite --hgvs --port 3337

VEP guesses the genomic location based on this HGVS input (17:7565261), and identifies that overlapping transcript ENST00000413465 has a protein product. However, the 285th amino acid of this transcript is not E, but Y. The alternate allele is guessed by VEP from a collection of options that it has. For example, with the input HGVS 'TP53:p.M237I’, then VEP has 3 potential alternate alleles it can use to do this, by converting the given ATG to one of ATA, ATC or ATT.

While VEP supports HGVS input, due to the complexity of HGVS and the variety of ways in which people use it, then we require that input HGVS is relative to genomic or transcript coordinates. In protein cases, we give a best guess where we can, but this is not guaranteed.

Sorry that I couldn’t be of more help.

Kind Regards,
Andrew


> On 14 Dec 2018, at 18:00, David Tamborero <david.tamborero at gmail.com> wrote:
> 
> Hi there, 
> 
> regarding the conversion from protein to genomic representation supported by VEP, I ve found a funny case; if I input 
> 
> TP53:p.E285V
> 
> VEP gives as output (vcf format)
> 
> 17    7565261    TP53:p.E285V    T    A
> 
> And then if I input to VEP that vcf entry,  I obtain  two TP53 protein annotations:
> 
> downstream_gene_variant for ENST00000359597
> missense_variant for ENST00000413465
> 
> However, the missense variant is annotated as 285 Y/F   (and not the E/V that I had at the start !)
> 
> so it looks that some inconsistency happened here, not sure why. Am I missing some point ?
> 
> thanks in advance!
> d
> 
> 
> 
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