<div dir="ltr"><div dir="ltr"><div>thanks for your answer!</div><div><br></div><div>mmm i understand that the protein representation can lead to a non-univocal genomic mapping, but i m unsure of why VEP tries to infer the genomic coordinates without considering the passed aminoacid of reference, (if this is what is happening !). Note that this particular aminoacid change (TP53:p.E285V) maps to a unique genomic missense mutation in all TP53 transcripts. <br></div><div><br></div><div>FYI (likely you know it), but when the mapping is not univocal, is not uncommon for other tools dealing with HGVS to give a guess --which is normally the 'most probable' based on different metrics-- as a first 'hit' (and detail the rest). This is specially needed when dealing with indels. <br></div><div><br></div><div>Although maybe this is too complicated for VEP. However, I m still not finding a good way for --by using your tools-- passing from HGVS protein representation to genomic coordinates (in 'vcf format', meaning chr pos ref alt). This is not an uncommon need in the field. If I may use this forum to ask, are you planning to support that in e.g. one of your API (i.e. like the 'hgvs conversor' but supporting the vcf-like output)?</div><div><br></div><div>many thanks for your time (and your work!)</div><div>best regards from Stockholm</div><div>d<br></div></div></div><br><div class="gmail_quote"><div dir="ltr">El dom., 16 dic. 2018 a las 14:19, Andrew Parton (<<a href="mailto:aparton@ebi.ac.uk">aparton@ebi.ac.uk</a>>) escribió:<br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div style="overflow-wrap: break-word;"><span>Hi David,</span><span><br></span><span><br></span><span></span><span>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: </span><span>perl vep -id 'TP53:p.E285V' --database --force_overwrite --hgvs --port 3337</span><span><br></span><span><br></span><span>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.<br></span><span><br></span><span>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.<br></span><span><br></span><span>Sorry that I couldn’t be of more help.<br></span><span><br></span><div><span>Kind Regards,</span></div><div><span style="background-color:rgb(255,255,255)">Andrew<br></span><br><br><blockquote type="cite">On 14 Dec 2018, at 18:00, David Tamborero <<a href="mailto:david.tamborero@gmail.com" target="_blank">david.tamborero@gmail.com</a>> wrote:<br><br>Hi there, <br><br>regarding the conversion from protein to genomic representation supported by VEP, I ve found a funny case; if I input <br><br>TP53:p.E285V<br><br>VEP gives as output (vcf format)<br><br>17 7565261 TP53:p.E285V T A<br><br>And then if I input to VEP that vcf entry, I obtain two TP53 protein annotations:<br><br>downstream_gene_variant for ENST00000359597<br>missense_variant for ENST00000413465<br><br>However, the missense variant is annotated as 285 Y/F (and not the E/V that I had at the start !)<br><br>so it looks that some inconsistency happened here, not sure why. Am I missing some point ?<br><br>thanks in advance!<br>d<br><br><br><br>_______________________________________________<br>Dev mailing list <a href="mailto:Dev@ensembl.org" target="_blank">Dev@ensembl.org</a><br>Posting guidelines and subscribe/unsubscribe info: <a href="http://lists.ensembl.org/mailman/listinfo/dev" target="_blank">http://lists.ensembl.org/mailman/listinfo/dev</a><br>Ensembl Blog: <a href="http://www.ensembl.info/" target="_blank">http://www.ensembl.info/</a><br></blockquote><br></div></div>_______________________________________________<br>
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