license:cc-by-nc-sa-4.0 biology region:us
---
license: cc-by-nc-sa-4.0
tags:
- biology
configs:
- config_name: gene_hg19
  data_files: "AlphaMissense_gene_hg19.csv"
- config_name: gene_hg38
  data_files: "AlphaMissense_gene_hg38.csv"
---

_Note: this database has been uploaded by Hugging Face staff. Please see the original paper, repo, and hosted database below for any questions._

# Google DeepMind AlphaMissense Database

<img src="https://www.science.org/cms/10.1126/science.adg7492/asset/e028b855-19a9-40ab-a39f-759afedb5b22/assets/images/large/science.adg7492-fa.jpg" alt="drawing" width="600"/>

- **Paper:** https://www.science.org/doi/10.1126/science.adg7492
- **Github Repo:** https://github.com/google-deepmind/alphamissense
- **Original Database:** https://console.cloud.google.com/storage/browser/dm_alphamissense


## File descriptions
* **AlphaMissense_hg19.tsv.gz, AlphaMissense_hg38.tsv.gz**: Predictions for all possible single nucleotide missense variants (71M) from 19k human
protein-coding genes (canonical transcripts) for both hg19 and hg38 coordinates. These
files are sorted by genomic coordinates.
* **AlphaMissense_gene_hg19.tsv.gz, AlphaMissense_gene_hg38.tsv.gz**: Gene-level average predictions, which were computed by taking the mean
alphamissense_pathogenicity over all possible missense variants in a transcript
(canonical transcript).
* **AlphaMissense_aa_substitutions.tsv.gz**: Predictions for all possible single amino acid substitutions within 20k UniProt canonical
isoforms (216M protein variants). These are a superset of the amino acid substitutions
induced by single nucleotide missense variants. This file uses UniProt accession
numbers for proteins and does not have genomic coordinates.
* **AlphaMissense_isoforms_hg38.tsv.gz**: Predictions for all possible missense variants for 60k non-canonical transcript isoforms
(hg38, GENCODE V32). This file has transcript_id but no UniProt accession numbers.
Predictions for non-canonical isoforms were not thoroughly evaluated and should be
used with caution. This file is sorted by genomic coordinates.
* **AlphaMissense_isoforms_aa_substitutions.tsv.gz**: Predictions for all possible single amino acid substitutions for 60k non-canonical
transcript isoforms (GENCODE V32). These are a superset of the amino acid
substitutions induced by single nucleotide missense variants.This file has transcript_id
but no UniProt accession numbers.

All transcript annotations are based on GENCODE V27 (hg19) or V32 (hg38).

Canonical transcripts are defined as described in the publication.

All files are compressed with bgzip.


## Column descriptions

**Note**: Not all columns are present in every file.

- **CHROM**  
  The chromosome as a string: `chr<N>`, where N is one of [1-22, X, Y, M].

- **POS**  
  Genome position (1-based).

- **REF**  
  The reference nucleotide (GRCh38.p13 for hg38, GRCh37.p13 for hg19).

- **ALT**  
  The alternative nucleotide.

- **genome**  
  The genome build, hg38 or hg19.

- **uniprot_id**  
  UniProtKB accession number of the protein in which the variant induces a single amino-acid substitution (UniProt release 2021_02).

- **transcript_id**  
  Ensembl transcript ID from GENCODE V27 (hg19) or V32 (hg38).

- **protein_variant**  
  Amino acid change induced by the alternative allele, in the format `<Reference amino acid><POS_aa><Alternative amino acid>` (e.g. V2L). POS_aa is the 1-based position of the residue within the protein amino acid sequence.

- **am_pathogenicity**  
  Calibrated AlphaMissense pathogenicity scores (ranging between 0 and 1), which can be interpreted as the predicted probability of a variant being clinically pathogenic.

- **am_class**  
  Classification of the `protein_variant` into one of three discrete categories: 'likely_benign', 'likely_pathogenic', or 'ambiguous'. These are derived using the following thresholds: 'likely_benign' if `alphamissense_pathogenicity` < 0.34; 'likely_pathogenic' if `alphamissense_pathogenicity` > 0.564; and 'ambiguous' otherwise.

- **mean_am_pathogenicity**  
  The average `alphamissense_pathogenicity` of all missense variants per transcript.

## Citation/license and disclaimer

AlphaMissense Database Copyright (2023) DeepMind Technologies Limited. All predictions are provided for non-commercial research use only under [CC BY-NC-SA license](https://creativecommons.org/licenses/by-nc-sa/4.0/).  
Researchers interested in predictions not yet provided, and for non-commercial use, can send an expression of interest to [alphamissense@google.com](mailto:alphamissense@google.com).

## Disclaimer

The AlphaMissense Database and other information provided on this site is for theoretical modelling only, caution should be exercised in use. It is provided “as-is” without any warranty of any kind, whether express or implied. For clarity, no warranty is given that use of the information shall not infringe the rights of any third party. The information provided is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. The predictions in the AlphaMissense Database are predictions only, with varying levels of confidence and should be interpreted carefully.

## Citation

If you use this resource for your research please cite the following publication:  
“Accurate proteome-wide missense variant effect prediction with AlphaMissense”  
Jun Cheng, Guido Novati, Joshua Pan, Clare Bycroft, Akvilė Žemgulytė, Taylor Applebaum, Alexander Pritzel, Lai Hong Wong, Michal Zielinski, Tobias Sargeant, Rosalia G. Schneider, Andrew W. Senior, John Jumper, Demis Hassabis, Pushmeet Kohli, Žiga Avsec

Use of the AlphaMissense Database is subject to [Google Cloud Platform Terms of Service](https://cloud.google.com/terms).
