rs199475673
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP3PM2
This summary comes from the ClinGen Evidence Repository: The c.689T>G (p.Val230Gly) variant in PAH was reported to the McGill PAHdb by Carducci in 1999, but has not been found in the literature. This variant is absent in population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA229692/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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.689T>G | p.Val230Gly | missense_variant | 6/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.689T>G | p.Val230Gly | missense_variant | 7/14 | ||
PAH | XM_017019370.2 | c.689T>G | p.Val230Gly | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.689T>G | p.Val230Gly | missense_variant | 6/13 | 1 | NM_000277.3 | P1 | |
PAH | ENST00000549111.5 | n.785T>G | non_coding_transcript_exon_variant | 6/6 | 1 | ||||
PAH | ENST00000307000.7 | c.674T>G | p.Val225Gly | missense_variant | 7/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461754Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727208
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Aug 20, 2020 | The c.689T>G (p.Val230Gly) variant in PAH was reported to the McGill PAHdb by Carducci in 1999, but has not been found in the literature. This variant is absent in population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: 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