rs62508595
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM3PM2PP4PP3
This summary comes from the ClinGen Evidence Repository: The c.1069T>G (p.Cys357Gly) variant in PAH has been reported in 1 individual with classic PKU in trans with pathogenic variant p.R176X (PMID:11139255). This variant is absent in population databases. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA229329/MONDO:0009861/006
Frequency
Consequence
ENST00000553106.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.1069T>G | p.Cys357Gly | missense_variant | 11/13 | ENST00000553106.6 | NP_000268.1 | |
PAH | NM_001354304.2 | c.1069T>G | p.Cys357Gly | missense_variant | 12/14 | NP_001341233.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.1069T>G | p.Cys357Gly | missense_variant | 11/13 | 1 | NM_000277.3 | ENSP00000448059 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461472Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727082
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Pathogenic:1
Likely pathogenic, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Jun 05, 2020 | The c.1069T>G (p.Cys357Gly) variant in PAH has been reported in 1 individual with classic PKU in trans with pathogenic variant p.R176X (PMID: 11139255). This variant is absent in population databases. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, 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