Missing AlphaMissense output for some variants

[sandylamwy]

Hi, I found quite a proportion of missense variants in my input vcf file to have AlphaMissense score missing in the VEP output. Further checking found that it is not just the issue of the AlphaMissense VEP plugin, but also in the VEP web query, and even in the dbNSFP v5.3.1 web query. However, I was able to find the AlphaMissense score in the UCSC browser, also the spliceAI lookup of Broad Institute.

System

• VEP version: 115.2
• VEP Cache version: 115 (GRCh38)

Relevant VEP command line:
--gencode_primary
--mane
--pick
--plugin AlphaMissense,file=${plugin_db}/alphamissense/AlphaMissense_hg38.tsv.gz \

Examples of variant with no AlphaMissense output:
chr2-178527212-G-C
chr3-38550616-C-T
chr12-2115266-A-G

Thank you for your advice.

[nakib103]

Hi @sandylamwy,

Thanks for your query. I will check and get back to you.

Regards,
Nakib

[nakib103]

Hi @sandylamwy,

I can see the AlphaMissense score for the first two variants in the VEP web results. Can you check if you have given the correct input.

For the third variant, I don't see any AlphaMissense score in VEP result in above job but it is similar in UCSC browser too (the track is empty for all four alternate allele). And, certainly enough the file provided does not contain any score in that region -

% tabix -s 1 -b 2 -e 2 AlphaMissense_hg38.tsv.gz 
% tabix AlphaMissense_hg38.tsv.gz chr2:2115264-2115268
%

[sandylamwy]

Thank you so much Nakib for your prompt investigation. From your VEP web results I can see that AlphaMissense scores are outputted for non-MANE transcript of the 1st and 2nd variants. When only MANE transcript is chosen, there is no AlphaMissense output, despite I didn't specify "transcript_match=1" in the AlphaMissense plugin command line.

[nakib103]

Thanks for flagging that! I have added above PR to fix the issue.