[ensembl-dev] VEP Annotation and reading frame

[ptashkir at mskcc.org]

Hi,


I'm looking for any insight into an issue we are having with the annotation of missense variants in MAP3K14. It appears that after exon 1, a different reading frame is selected for different exons.

Please see the test case below, using the VEP web interface. We are interested in RefSeq annotations, but even the ENSMBL annotations are also confusing. Results are the same for our local install of version 82.

For the RefSeq annotation, how is the reading frame selected? The variant is annotated as  (p.W406C) , why is it not G407S? After exon 1, it looks like reading frame is not consistent from exon to exon. Splicing mutations are properly annotated however.

All ensmbl annotations are listed as non-coding. You'll also notice on the provided IGV screenshot that the MAP3K14-AS1 non-coding transcript is well downstream of this exon6 mutation. Any insight is greatly appreciated. Thanks!


Test case: Ensembl GRCh37 release 84 - March 2016
####################
INPUT:
####################
17 43362250 . C A . . .


######### VEP ANNOTATIONS RefSeq and ENSMBL: ##################################

NM_003954.3 protein_coding  6/16 - NM_003954.3:c.1218G>T NP_003945.2:p.Trp406Cys

ENST00000376926 processed_transcript 4/8 - ENST00000376926.4:n.568G>T -

ENST00000344686 processed_transcript 7/17 - ENST00000344686.2:n.1325G>T -

ENST00000587332 processed_transcript 6/16 - ENST00000587332.1:n.1319G>T -



Thanks,

Ryan Ptashkin
Computational Biologist
Memorial Sloan Kettering Cancer Center
ptashkir at mskcc.org<mailto:ptashkir at mskcc.org>


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