TABLE 3.
Pathogenic and likely pathogenic 5′ UTR variants by proposed or validated mechanism (n = 68).
| Variant a | Gene | Classifications(s) (ClinVar) | Classification (present study) |
|---|---|---|---|
| Translation: Impact on existing regulatory uORF (n = 10) | |||
| NM_000460.3:c.-31G>T | THPO | P | LP |
| NM_000460.3:c.-47del | THPO | P | LP |
| NM_005144.4:c.-218A>G | HR | P | LP |
| NM_005144.4:c.-249C>G | HR | P | LP |
| NM_005144.4:c.-315C>T | HR | P | LP |
| NM_005144.4:c.-320T>C | HR | P | P |
| NM_005144.4:c.-320T>A | HR | LP | LP |
| NM_000280.4:c.-118_-117del | PAX6 | P/LP | P |
| NM_000280.4:c.-122dup | PAX6 | LP | P |
| NM_004064.4:c.-454_-451del | CDKN1B | P | LP |
| Translation: introduction of novel upstream start codon (n = 13) | |||
| NM_006516.2:c.-107G>A | SLC2A1 | LP | P |
| NM_001204.7:c.-947_-946delinsAT | BMPR2 | P | LP |
| NM_000939.3:c.-11C>A | POMC | P | LP |
| NM_000313.3:c.-39C>T | PROS1 | P | LP |
| NM_054027.5:c.-11C>T | ANKH | P | LP |
| NM_001131005.2:c.-8C>T | MEF2C | P | LP |
| NM_001131005.2:c.-26C>T | MEF2C | P | LP |
| NM_001131005.2:c.-66A>T | MEF2C | P | LP |
| NM_001114753.2:c.-127C>T | ENG | P/LP | LP |
| NM_012203.2:c.-4_-3delinsAT | GRHPR | P | LP |
| NM_001025295.2:c.-14C>T | IFITM5 | P | P |
| NM_000518.4:c.-29G>A | HBB | P | LP |
| NM_006767.3:c.-38T>A | LZTR1 | P/LP | LP |
| Translation: altered mRNA-protein interaction (n = 12) | |||
| NM_002032.2:c.-164A>T | FTH1 | P | LP |
| NM_000146.3:c.-168G>A | FTL | P | P |
| NM_000146.3:c.-168G>C | FTL | P | P |
| NM_000146.3:c.-168G>T | FTL | P | P |
| NM_000146.3:c.-167C>T | FTL | P | P |
| NM_000146.3:c.-164C>A | FTL | P | LP |
| NM_000146.3:c.-164C>T | FTL | P | P |
| NM_000146.3:c.-161C>G | FTL | P | LP |
| NM_000146.3:c.-161C>T | FTL | P | P |
| NM_000146.3:c.-160A>G | FTL | P | LP |
| NM_000146.3:c.-157G>A | FTL | P | P |
| NM_000146.3:c.-149G>C | FTL | P | LP |
| Transcription: altered promoter activity (n = 14) | |||
| NM_003051.3:c.-202G>A | SLC16A1 | P | LP |
| NM_005105.4:c.-21G>A | RBM8A | P/LP | P |
| NM_000551.3:c.-75_-55del | VHL | LP | LP |
| NM_000037.3:c.-73_-72del | ANK1 | P | LP |
| NM_000375.2:c.-203T>C | UROS | P | LP |
| NM_014915.2:c.-127A>T | ANKRD26 | P/LP | P |
| NM_014915.2:c.-127A>G | ANKRD26 | P | LP |
| NM_014915.2:c.-127A>C | ANKRD26 | LP | LP |
| NM_014915.2:c.-128G>A | ANKRD26 | P | P |
| NM_000518.4:c.-18C>G | HBB | P | LP |
| NM_001814.5:c.-55C>A | CTSC | P | LP |
| NM_017671.4:c.-20A>G | FERMT1 | P | LP |
| NM_000026.3:c.-49T>C | ADSL | LP | LP |
| NM_000133.3:c.-17A>G | F9 | P | LP |
| Transcription: altered promoter methylation (n = 2) | |||
| NM_007294.3:c.-107A>T | BRCA1 | P | LP |
| NM_000249.3:c.-27C>A | MLH1 | P/LP | LP |
| Transcription: splicing (n = 4) | |||
| NM_021067.4:c.-60A>G | GINS1 | P | LP |
| NM_021067.4:c.-48C>G | GINS1 | P | P |
| NM_000451.3:c.-19G>A | SHOX | P/LP | LP |
| NM_000166.5:c.-17G>A | GJB1 | P/LP | LP |
| Undetermined mechanism (n = 13) | |||
| NM_005105.4:c.-19G>A | RBM8A | P | LP |
| NM_022787.3:c.-69C>T | NMNAT1 | P | LP |
| NM_173546.2:c.-158C>T | KLHDC8B | P | P |
| NM_133433.4:c.-321_-320delinsA | NIPBL | P | LP |
| NM_014915.2:c.-126T>G | ANKRD26 | P | LP |
| NM_014915.2:c.-126T>C | ANKRD26 | P/LP | LP |
| NM_014915.2:c.-128G>T | ANKRD26 | LP | LP |
| NM_014915.2:c.-128G>C | ANKRD26 | LP | LP |
| NM_014915.2:c.-134G>A | ANKRD26 | P/LP | LP |
| NM_000518.4:c.-50A>C | HBB | P | LP |
| NM_000133.3:c.-22T>C | F9 | P | LP |
| NM_001551.3:c.-57_-55delinsAA | IGBP1 | P | LP |
| NM_000166.5:c.-103C>T | GJB1 | P | LP |
a
Variant HGVS, nomenclature is provided for the APPRIS-defined principal transcript.
LP, likely pathogenic; P, pathogenic; P/LP, P and LP, classifications across multiple submitters; uORF, upstream open reading frame; UTR, untranslated region.