Predictions for AlphaMissense

• DOI: 10.5281/zenodo.8208688
• Publication Date: 2023-09-19
• Authors: Jun Cheng; Guido Novati; Joshua Pan; Clare Bycroft; Akvilė Žemgulytė; Taylor Applebaum; Alexander Pritzel; Lai Hong Wong; Michał Zieliński; Tobias Sargeant; Rosalia G. Schneider; Andrew Senior; John Jumper; Demis Hassabis; Pushmeet Kohli; Žiga Avsec

This repository provide AlphaMissense predictions. For questions about AlphaMissense or the prediction Database please email [e-mail]. 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 that not all columns are present in every file. CHROM The chromosome as a string: chr, 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 (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. License Copyright (2023) DeepMind Technologies Limited All materials are licensed under the Creative Commons Attribution 4.0 International License (CC-BY) (the “License”). You may obtain a copy of the License at: https://creativecommons.org/licenses/by/4.0/legalcode. Unless required by applicable law or agreed to in writing, all materials distributed under the License are distributed on an "AS IS" AND “AS AVAILABLE” BASIS, WITHOUT REPRESENTATIONS, WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. See the License for the specific language governing permissions and limitations under the License. Researchers interested in predictions not yet provided can send an expression of interest to [e-mail]. Disclaimer This is not an officially supported Google product The AlphaMissense Database contains predictions with varying levels of confidence, caution should be exercised in use. 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. AlphaMissense has not been validated for, and is not approved for, any clinical use. 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 Data format samples AlphaMissense_hg19.tsv.gz, AlphaMissense_hg38.tsv.gz #CHROM POS REF ALT genome uniprot_id transcript_id protein_variant am_pathogenicity am_class chr1 69094 G T hg38 Q8NH21 ENST00000335137.4 V2L 0.2937 likely_benign chr1 69094 G C hg38 Q8NH21 ENST00000335137.4 V2L 0.2937 likely_benign chr1 69094 G A hg38 Q8NH21 ENST00000335137.4 V2M 0.3296 likely_benign chr1 69095 T C hg38 Q8NH21 ENST00000335137.4 V2A 0.2609 likely_benign AlphaMissense_aa_substitutions.tsv.gz uniprot_id protein_variant am_pathogenicity am_class A0A024R1R8 M1A 0.4673 ambiguous A0A024R1R8 M1C 0.3828 ambiguous AlphaMissense_gene_hg19.tsv.gz, AlphaMissense_gene_hg38.tsv.gz transcript_id mean_am_pathogenicity ENST00000000233.5 0.7422697635438503 ENST00000000412.3 0.37834258163288265 ENST00000001008.4 0.4222901115567318 ENST00000001146.2 0.4666058543393151 AlphaMissense_isoforms_hg38.tsv.gz #CHROM POS REF ALT genome transcript_id protein_variant am_pathogenicity am_class chr1 65568 A C hg38 ENST00000641515.2 K2Q 0.0938 likely_benign chr1 65568 A G hg38 ENST00000641515.2 K2E 0.0766 likely_benign chr1 65569 A G hg38 ENST00000641515.2 K2R 0.0756 likely_benign chr1 65569 A T hg38 ENST00000641515.2 K2M 0.1732 likely_benign AlphaMissense_isoforms_aa_substitutions.tsv.gz transcript_id protein_variant am_pathogenicity am_class ENST00000000442.11 M1A 0.2808 likely_benign ENST00000000442.11 M1C 0.1724 likely_benign ENST00000000442.11 M1D 0.7278 likely_pathogenic ENST00000000442.11 M1E 0.5328 ambiguous