Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document
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  • See Evidence submitted by expert panel for details.

CA6748745

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e6f92dc4-515e-4f21-a00a-a068781a7c73
Approved on: 2022-12-09
Published on: 2022-12-09

HGVS expressions

NM_001354304.2:c.1084C>T
NC_000012.12:g.102843761G>A
CM000674.2:g.102843761G>A
NC_000012.11:g.103237539G>A
CM000674.1:g.103237539G>A
NC_000012.10:g.101761669G>A
NG_008690.1:g.78842C>T
NG_008690.2:g.119650C>T
ENST00000553106.6:c.1084C>T
ENST00000307000.7:c.1069C>T
ENST00000549247.6:n.843C>T
ENST00000551114.2:n.746C>T
ENST00000553106.5:c.1084C>T
ENST00000635477.1:n.188C>T
ENST00000635528.1:n.599C>T
NM_000277.1:c.1084C>T
NM_000277.2:c.1084C>T
NM_001354304.1:c.1084C>T
NM_000277.3:c.1084C>T
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Likely Pathogenic

Met criteria codes 4
PP4 PP3 PM2 PM3
Not Met criteria codes 1
PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
This c.1084C>T (p.Pro362Ser) variant in PAH was reported in a patient with classic PKU in trans with the pathogenic variant p.Arg413Pro (PMID: 28982351). This variant was present at an extremely low frequency in ExAC and absent in the gnomAD population database. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM3, PM2, PP3, PP4.
Met criteria codes
PP4
Variant was detected in a patient affected with cPKU. Variable sites in patient genes were aligned with the corresponding sites from the respective parents. This was seen in trans with a pathogenic variant listed in ClinVar. Those with BH4 cofactor deficiency were excluded PMID: 28982351
PP3
Predicted to be damaging (SIFT), probably damaging (PolyPhen2), Disease causing (MutationTaster). REVEL=0.796
PM2
Present in European (non-Finnish) populations at a frequency of 0.00001 (ExAC). This variant is absent from the population database gnomAD.
PM3
This variant was detected in trans with the ClinVar reported pathogenic variant p.Arg413Pro in a patient with cPKU (PMID: 28982351). points=1.
Not Met criteria codes
PM5
Tother variants one likely pathogenic (p.P362R) and one uncategorized (p.P362T) have been documented in ClinVar at this amino acid residue.
Curation History
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