rs199475569
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3PP4_ModeratePM2
This summary comes from the ClinGen Evidence Repository: The c.190C>A (p.His64Asn) variant in PAH has been reported in a Danish mild PKU patient. Serum Phe levels exceeded 600 umol/L and other causes of hyperphenylalaninemia had been ruled out. It was In cis with p.T63P. PMID:8406445. The c.190C>A variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, and MutationTaster. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA229475/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 | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.190C>A | p.His64Asn | missense_variant | 3/13 | ENST00000553106.6 | |
LOC124902999 | XR_007063428.1 | n.863-9801G>T | intron_variant, non_coding_transcript_variant | ||||
PAH | NM_001354304.2 | c.190C>A | p.His64Asn | missense_variant | 4/14 | ||
PAH | XM_017019370.2 | c.190C>A | p.His64Asn | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.190C>A | p.His64Asn | missense_variant | 3/13 | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461376Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727038
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Dec 10, 2018 | The c.190C>A (p.His64Asn) variant in PAH has been reported in a Danish mild PKU patient. Serum Phe levels exceeded 600 umol/L and other causes of hyperphenylalaninemia had been ruled out. It was In cis with p.T63P. PMID: 8406445. The c.190C>A variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, and MutationTaster. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3. - |
not provided Other:1
not provided, no classification provided | literature only | DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at