Answers.Body: <p>The <a href="https://github.com/Ensembl/VEP_plugins/blob/release/96/dbNSFP.pm" rel="nofollow noreferrer">dbNSFP plugin</a> from VEP accesses tables of data for each variant from dbNSFP and pulls out the values. dbNSFP provide their SIFT scores in that format: a score for every transcript affected by the variant, all on one line. The lookup is just for the variant, not for the variant/transcript combo, so they provide scores for all variant/transcript combos. You can also get a column that gives you a list of the transcripts or proteins (Ensembl_transcriptid or Ensembl_proteinid) in order so you know which score goes with which transcript.</p>
  
  <p>A better way to get SIFT scores with VEP is to get them directly from VEP, rather than using dbNSFP. This will get the SIFT score that goes with the transcript on the line with the relevant transcript.</p>
  
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2019-04-10T12:18:54.350Z
Answers.Text: I am guessing the dots are there for cases where dbNSFP doesn't have a value for the relevant transcript, right?
Answers.UserDisplayName: terdon
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2019-04-10T13:00:07.737Z
Answers.Text: Yes, that's it. Could be that the variant isn't missense in that transcript.
Answers.UserDisplayName: Emily_Ensembl
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2019-04-10T10:05:19.823Z
Answers.LastActivityDate: 2019-04-10T10:45:58.443Z
Answers.LastEditDate: 2019-04-10T10:45:58.443Z
Answers.UserDisplayName: Emily_Ensembl
Answers.Body: <p>The first gene you mention, ENSG00000196924, actually <a href="https://varsome.com/variant/hg38/rs371839875" rel="nofollow noreferrer">has 6 transcripts</a> (link to the VarSome.com page of variant rs371839875), not 5. It's just that one of them is non-coding:</p>
  
  <p><a href="https://i.sstatic.net/rUyYq.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/rUyYq.png" alt="VarSome genome browser showing transcripts"></a></p>
  
  <p>So the Sift scores you see are indeed one per transcript, it's just that there are 6 because dbNSFP also includes a score for the non-coding transcript of the gene. </p>
  
  <p>The dots are just there as placeholders, they mean there was no value associated with that transcript. Many tools will show some sort of symbol instead of an empty field both for clarity and for practical technical reasons. </p>
  
  <p>Visiting the <a href="https://varsome.com/variant/hg38/rs371839875" rel="nofollow noreferrer">variant's page</a> on VarSome gives you a clearer picture since we collapse the identical scores and also include the converted rankscore provided by dbNSFP so you can have a single number for your variant:</p>
  
  <p><a href="https://i.sstatic.net/cyfSO.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/cyfSO.png" alt="VarSome screenshot showing SIFT score"></a></p>
  
  <hr>
  
  <p><strong>Disclaimer</strong>: I work for the company behind <a href="https://varsome.com" rel="nofollow noreferrer">VarSome</a>, but it's a free tool. You need to pay to annotate VCF files (unlike the 100% free VEP), but it's free to use as a lookup tool for single variants.</p>
  
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2019-04-10T12:06:38.850Z
Answers.LastActivityDate: 2019-04-10T12:13:28.950Z
Answers.LastEditDate: 2019-04-10T12:13:28.950Z
Answers.UserDisplayName: terdon
Body: <p>We have been experimenting with VEP (Variant Effect Predictor). One of the meta data attributes that we are interested in is the SIFT score, indeed when we apply the dbNSFP plug we get a column containing the scores (named SIFT_score). However, I don't understand why there are sometimes dots or multiple values in the fields. For example, the gene ENSG00000196924 below has 5 transcripts:</p>
  
  <p><a href="https://i.sstatic.net/8FdyW.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/8FdyW.png" alt="DataFrame of VEP output"></a></p>
  
  <p>The SIFT_score column contains several values, not 1 per transcript/rs-number...</p>
  
  <p>Here is another example that confuses me (I added the SIFT_pred column this time):</p>
  
  <p><a href="https://i.sstatic.net/Jmjyt.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/Jmjyt.png" alt="DataFrame of another gene with mutations"></a></p>
  
  <p>There are two mutations, the lower one can be expressed in 4 transcripts and I thus understand that there can be 4 SIFT scores, but why are all for in given in every row? Is the first one the SIFT_score for the first transcript?</p>
  
  <p>One last example, again 4 transcripts, but now 2 of the scores are dots, what does that mean?</p>
  
  <p><a href="https://i.sstatic.net/Lo0Qb.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/Lo0Qb.png" alt="And another pd.DataFrame"></a></p>
  
  <p>I have been looking for quite some time now how to interpret this data, any help is appreciated.</p>
  
Tags: <ngs><variant-calling>
Title: VEP output SIFT_score unclear
ThreadText: # VEP output SIFT_score unclear
  
  (Asked by: username_0 on 2019-04-10)
  
  We have been experimenting with VEP (Variant Effect Predictor). One of the meta data attributes that we are interested in is the SIFT score, indeed when we apply the dbNSFP plug we get a column containing the scores (named SIFT\_score). However, I don't understand why there are sometimes dots or multiple values in the fields. For example, the gene ENSG00000196924 below has 5 transcripts:
  
  [![DataFrame of VEP output](https://i.sstatic.net/8FdyW.png)](https://i.sstatic.net/8FdyW.png)
  
  The SIFT\_score column contains several values, not 1 per transcript/rs-number...
  
  Here is another example that confuses me (I added the SIFT\_pred column this time):
  
  [![DataFrame of another gene with mutations](https://i.sstatic.net/Jmjyt.png)](https://i.sstatic.net/Jmjyt.png)
  
  There are two mutations, the lower one can be expressed in 4 transcripts and I thus understand that there can be 4 SIFT scores, but why are all for in given in every row? Is the first one the SIFT\_score for the first transcript?
  
  One last example, again 4 transcripts, but now 2 of the scores are dots, what does that mean?
  
  [![And another pd.DataFrame](https://i.sstatic.net/Lo0Qb.png)](https://i.sstatic.net/Lo0Qb.png)
  
  I have been looking for quite some time now how to interpret this data, any help is appreciated.
  
  **Tags:** ngs, variant-calling
  
  
  ---
  
  ## 2 answers
  
  ### Answer by username_1 on 2019-04-10. Score: 3
  
  The [dbNSFP plugin](https://github.com/Ensembl/VEP_plugins/blob/release/96/dbNSFP.pm) from VEP accesses tables of data for each variant from dbNSFP and pulls out the values. dbNSFP provide their SIFT scores in that format: a score for every transcript affected by the variant, all on one line. The lookup is just for the variant, not for the variant/transcript combo, so they provide scores for all variant/transcript combos. You can also get a column that gives you a list of the transcripts or proteins (Ensembl\_transcriptid or Ensembl\_proteinid) in order so you know which score goes with which transcript.
  
  A better way to get SIFT scores with VEP is to get them directly from VEP, rather than using dbNSFP. This will get the SIFT score that goes with the transcript on the line with the relevant transcript.
  
  > **Comments:**
  > **username_2**: I am guessing the dots are there for cases where dbNSFP doesn't have a value for the relevant transcript, right?  
  > **username_1**: Yes, that's it. Could be that the variant isn't missense in that transcript.  
  
  ---
  
  ### Answer by username_2 on 2019-04-10. Score: 3
  
  The first gene you mention, ENSG00000196924, actually [has 6 transcripts](https://varsome.com/variant/hg38/rs371839875) (link to the VarSome.com page of variant rs371839875), not 5. It's just that one of them is non-coding:
  
  [![VarSome genome browser showing transcripts](https://i.sstatic.net/rUyYq.png)](https://i.sstatic.net/rUyYq.png)
  
  So the Sift scores you see are indeed one per transcript, it's just that there are 6 because dbNSFP also includes a score for the non-coding transcript of the gene.
  
  The dots are just there as placeholders, they mean there was no value associated with that transcript. Many tools will show some sort of symbol instead of an empty field both for clarity and for practical technical reasons.
  
  Visiting the [variant's page](https://varsome.com/variant/hg38/rs371839875) on VarSome gives you a clearer picture since we collapse the identical scores and also include the converted rankscore provided by dbNSFP so you can have a single number for your variant:
  
  [![VarSome screenshot showing SIFT score](https://i.sstatic.net/cyfSO.png)](https://i.sstatic.net/cyfSO.png)
  
  ---
  
  **Disclaimer**: I work for the company behind [VarSome](https://varsome.com), but it's a free tool. You need to pay to annotate VCF files (unlike the 100% free VEP), but it's free to use as a lookup tool for single variants.
  
  
  ---
  
  