rs1555209578
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PP4PM4PM3_StrongPM2
This summary comes from the ClinGen Evidence Repository: The c.124_126del (p.Lys42del) PAH variant has been reported in 2 patients with PAH deficiency, detected with the pathogenic PAH variant p.Arg111Ter (PMID:30050108) and the likely pathogenic PAH variant c.824C>T (PMID:27243974). A defect in BH4 metabolism was not excluded. This variant is absent from population databases. The protein length changes as a result of an in-frame deletion in a non-repeat region. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3_strong, PM4, PP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA658821284/MONDO:0009861/006
Frequency
Consequence
NM_000277.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.124_126del | p.Lys42del | inframe_deletion | 2/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.124_126del | p.Lys42del | inframe_deletion | 3/14 | ||
PAH | XM_017019370.2 | c.124_126del | p.Lys42del | inframe_deletion | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.124_126del | p.Lys42del | inframe_deletion | 2/13 | 1 | NM_000277.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727060
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Pathogenic:2Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 14, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 01, 2017 | - - |
Likely pathogenic, reviewed by expert panel | curation | ClinGen PAH Variant Curation Expert Panel | Oct 16, 2020 | The c.124_126del (p.Lys42del) PAH variant has been reported in 2 patients with PAH deficiency, detected with the pathogenic PAH variant p.Arg111Ter (PMID: 30050108) and the likely pathogenic PAH variant c.824C>T (PMID: 27243974). A defect in BH4 metabolism was not excluded. This variant is absent from population databases. The protein length changes as a result of an in-frame deletion in a non-repeat region. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3_strong, PM4, PP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at