c9446936b026a803d97e7f5128404a327829fe2e max Sun Jul 19 00:01:22 2026 -0700 ClinVar Mapped: add Pfam-domain mapping method Maps ClinVar coding variants through Pfam protein domains as a second method under the clinvarMapped container. Each Pfam family's profile HMM gives a shared coordinate, so a variant inside a domain is projected to the residue in the same HMM match-state column in every other MANE Select gene carrying that domain, then mapped back to that gene's genomic codon. This links genes that share a domain without being paralogs (e.g. the SCN sodium channels and the CACNA1 calcium channels via Ion_trans). Each variant is shown at its 25 most conserved equivalents. Uses Pfam-A 38.2. Adds two alpha subtracks (Pfam Domain Variants, Pfam Domains), the hmmsearch/hmmalign build scripts, autoSql, makeDoc and description page, refs #37883 diff --git src/hg/makeDb/trackDb/human/hg38/clinvarMapped.ra src/hg/makeDb/trackDb/human/hg38/clinvarMapped.ra index 6526aa731aa..b08d8ebd216 100644 --- src/hg/makeDb/trackDb/human/hg38/clinvarMapped.ra +++ src/hg/makeDb/trackDb/human/hg38/clinvarMapped.ra @@ -1,60 +1,106 @@ track clinvarMapped compositeTrack on shortLabel ClinVar Mapped longLabel ClinVar coding variants mapped to related loci by sequence homology group phenDis visibility hide type bigBed -dataVersion Ensembl 116 paralogs, MANE Select 1.5, ClinVar as of build date +dataVersion Ensembl 116 paralogs, Pfam-A 38.2, MANE Select 1.5, ClinVar as of build date html clinvarMapped track clinvarMappedParalog parent clinvarMapped on shortLabel Paralog Variants longLabel ClinVar coding variants mapped to the equivalent residue of paralogous genes type bigBed 12 + bigDataUrl /gbdb/hg38/clinvarMapped/clinvarMappedParalog.bb itemRgb on noScoreFilter on maxItems 100000 urls vcvId="https://www.ncbi.nlm.nih.gov/clinvar/variation/$$/" sourceLocus="hgTracks?db=hg38&position=$$" mouseOver Mapped from ${sourceGene} ${sourceVariant} — ${clinSign} (${reviewStars} star)
Source residue ${srcRes}${sourceAaPos} in ${sourceGene}; aligned residue here is ${thisRes} (${residueMatch})
Ensembl paralog identity ${bioPercId}%, alignment identity ${alnPercId}% filterText.sourceGene * filterType.sourceGene wildcard filterLabel.sourceGene Source gene (wildcards allowed, e.g. SCN5A or SCN*) filterValues.clinSignCode PG|pathogenic,LP|likely pathogenic,CF|conflicting,VUS|uncertain,RF|risk factor,OT|other,LB|likely benign,BN|benign filterValuesDefault.clinSignCode PG,LP filterType.clinSignCode multipleListOr filterLabel.clinSignCode Clinical significance filterValues.residueMatch identical,similar,different filterType.residueMatch multipleListOr filterLabel.residueMatch Residue conservation filterValues.molConseq missense variant,nonsense,inframe deletion,inframe insertion,inframe indel,initiator codon variant,stop lost filterType.molConseq multipleListOr filterLabel.molConseq Source molecular consequence filterByRange.reviewStars on filter.reviewStars 0:4 filterLimits.reviewStars 0:4 filterLabel.reviewStars ClinVar review stars filterByRange.bioPercId on filter.bioPercId 0:100 filterLimits.bioPercId 0:100 filterLabel.bioPercId Ensembl paralog percent identity filterByRange.alnPercId on filter.alnPercId 0:100 filterLimits.alnPercId 0:100 filterLabel.alnPercId Alignment percent identity track clinvarMappedParalogAln parent clinvarMapped off shortLabel Paralog Alignments longLabel Paralog protein alignments used to map the variants type bigPsl bigDataUrl /gbdb/hg38/clinvarMapped/clinvarMappedParalogAln.bb visibility pack baseColorUseSequence lfExtra baseColorDefault diffBases showDiffBasesAllScales . showDiffBasesMaxZoom 10000.0 indelDoubleInsert on indelQueryInsert on + + track clinvarMappedPfam + parent clinvarMapped off + shortLabel Pfam Domain Variants + longLabel ClinVar coding variants mapped to the equivalent Pfam domain position in other genes + type bigBed 12 + + bigDataUrl /gbdb/hg38/clinvarMapped/clinvarMappedPfam.bb + itemRgb on + noScoreFilter on + maxItems 100000 + urls vcvId="https://www.ncbi.nlm.nih.gov/clinvar/variation/$$/" sourceLocus="hgTracks?db=hg38&position=$$" pfamAcc="https://www.ebi.ac.uk/interpro/entry/pfam/$$/" + mouseOver Mapped from ${sourceGene} ${sourceVariant} — ${clinSign} (${reviewStars} star)
${pfamId} domain position ${domainColumn}: source residue ${srcRes}${sourceAaPos} in ${sourceGene}, residue here is ${thisRes} in ${thisGene} (${residueMatch}) + filterText.sourceGene * + filterType.sourceGene wildcard + filterLabel.sourceGene Source gene (wildcards allowed, e.g. SCN5A or SCN*) + filterText.pfamId * + filterType.pfamId wildcard + filterLabel.pfamId Pfam domain (wildcards allowed) + filterValues.clinSignCode PG|pathogenic,LP|likely pathogenic,CF|conflicting,VUS|uncertain,RF|risk factor,OT|other,LB|likely benign,BN|benign + filterValuesDefault.clinSignCode PG,LP + filterType.clinSignCode multipleListOr + filterLabel.clinSignCode Clinical significance + filterValues.residueMatch identical,similar,different + filterType.residueMatch multipleListOr + filterLabel.residueMatch Residue conservation + filterValues.molConseq missense variant,nonsense,inframe deletion,inframe insertion,inframe indel,initiator codon variant,stop lost + filterType.molConseq multipleListOr + filterLabel.molConseq Source molecular consequence + filterByRange.reviewStars on + filter.reviewStars 0:4 + filterLimits.reviewStars 0:4 + filterLabel.reviewStars ClinVar review stars + + track clinvarMappedPfamAln + parent clinvarMapped off + shortLabel Pfam Domains (MANE) + longLabel Pfam domain footprints on MANE Select genes, evidence for the Pfam mapping + type bigBed 12 + + bigDataUrl /gbdb/hg38/clinvarMapped/clinvarMappedPfamAln.bb + visibility pack + filterText.pfamId * + filterType.pfamId wildcard + filterLabel.pfamId Pfam domain (wildcards allowed) + filterText.gene * + filterType.gene wildcard + filterLabel.gene Gene (wildcards allowed)