rs199475604
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PP3PM3PP4_ModeratePM2
This summary comes from the ClinGen Evidence Repository: The c.523C>T (p.Pro175Ser) variant in PAH has been reported in 1 individual with classic PKU (BH4 deficiency excluded) in trans with pathogenic variant p.R413P (PP4_Moderate, PM3; PMID:26322415). This variant is absent in population databases (PM2). Computational evidence support a deleterious effect (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA16020810/MONDO:0009861/006
Frequency
Consequence
NM_000277.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.523C>T | p.Pro175Ser | missense_variant | 6/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.523C>T | p.Pro175Ser | missense_variant | 7/14 | ||
PAH | XM_017019370.2 | c.523C>T | p.Pro175Ser | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.523C>T | p.Pro175Ser | missense_variant | 6/13 | 1 | NM_000277.3 | P1 | |
PAH | ENST00000549111.5 | n.619C>T | non_coding_transcript_exon_variant | 6/6 | 1 | ||||
PAH | ENST00000307000.7 | c.508C>T | p.Pro170Ser | missense_variant | 7/14 | 5 | |||
PAH | ENST00000551988.5 | n.544C>T | non_coding_transcript_exon_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Phenylketonuria Pathogenic:1Uncertain:1
Likely pathogenic, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Apr 08, 2019 | The c.523C>T (p.Pro175Ser) variant in PAH has been reported in 1 individual with classic PKU (BH4 deficiency excluded) in trans with pathogenic variant p.R413P (PP4_Moderate, PM3; PMID: 26322415). This variant is absent in population databases (PM2). Computational evidence support a deleterious effect (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at