rs751203209
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3PP4PM2PM3_Supporting
This summary comes from the ClinGen Evidence Repository: The c.870T>G (p.His290Gln) variant in PAH has been reported in one patient with classic PKU (BH4 deficiency not excluded; PP4; PMID:26210745). It was detected with known pathogenic variant p.R261Q, but parental testing was not reported/performed. This variant is absent from 1000G, ESP, ExAC and gnomAD. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.924. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3, PM3_supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA16020878/MONDO:0009861/006
Frequency
Consequence
NM_000277.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.870T>G | p.His290Gln | missense_variant | 8/13 | ENST00000553106.6 | NP_000268.1 | |
PAH | NM_001354304.2 | c.870T>G | p.His290Gln | missense_variant | 9/14 | NP_001341233.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.870T>G | p.His290Gln | missense_variant | 8/13 | 1 | NM_000277.3 | ENSP00000448059.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Pathogenic:1Uncertain:1
Likely pathogenic, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Dec 12, 2021 | The c.870T>G (p.His290Gln) variant in PAH has been reported in one patient with classic PKU (BH4 deficiency not excluded; PP4; PMID: 26210745). It was detected with known pathogenic variant p.R261Q, but parental testing was not reported/performed. Functional studies show low but measurable activities for tyrosine formation and greatly decreased the affinity for iron (PMID: 18477464). This variant is absent from 1000G, ESP, ExAC and gnomAD. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.924. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3, PM3_supporting, PS3_supporting. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at