Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000277.3(PAH):c.32T>A (p.Leu11Ter)

CA386303850

625287 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7eef4555-98b1-448b-99e1-a6686ee78092

HGVS expressions

NM_000277.3:c.32T>A

NM_000277.3(PAH):c.32T>A (p.Leu11Ter)

NM_000277.1:c.32T>A

NM_000277.2:c.32T>A

NM_001354304.1:c.32T>A

NM_001354304.2:c.32T>A

ENST00000307000.7:c.-116T>A

ENST00000546844.1:c.32T>A

ENST00000547319.1:n.343T>A

ENST00000549111.5:n.128T>A

ENST00000550978.6:n.16T>A

ENST00000551337.5:c.32T>A

ENST00000551988.5:n.121T>A

ENST00000553106.5:c.32T>A

ENST00000635500.1:n.29-4201T>A

NC_000012.12:g.102917099A>T

CM000674.2:g.102917099A>T

NC_000012.11:g.103310877A>T

CM000674.1:g.103310877A>T

NC_000012.10:g.101835007A>T

NG_008690.1:g.5504T>A

NG_008690.2:g.46312T>A

Pathogenic

PVS1 PM3 PM2 PP4_Moderate

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The p.L11* variant in PAH is a null variant (nonsense variant) in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It has been previously reported in one Ugyur proband (PMID: 31355225) with classic PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). The patient was compound heterozygous for the variant (confirmed by parental testing) and carried it in trans with the p.R413P variant (known pathogenic per PAH ClinGen working group) (PM3). It is also reported in ClinVar (ID 625287) as a de novo variant by one lab, in a case with PKU; no further information is given.

PVS1

The p.L11* variant in PAH is a null variant (nonsense variant) in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD.

PM3

It has been previously reported in one Ugyur proband (PMID: 31355225) with classic PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). The patient was compound heterozygous for the variant (confirmed by parental testing) and carried it in trans with the p.R413P variant (known pathogenic per PAH ClinGen working group) (PM3).

PM2

It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).

PP4_Moderate

It has been previously reported in one Ugyur proband (PMID: 31355225) with classic PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate).

Approved on: 2020-04-09

Published on: 2020-04-09

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