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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.1(PAH):c.716G>T (p.Gly239Val)

CA229711

102800 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: fb82abb9-c0f3-4901-acad-0e2a6de4b34d

HGVS expressions

NM_000277.1:c.716G>T

NM_000277.1(PAH):c.716G>T (p.Gly239Val)

NC_000012.12:g.102852941C>A

CM000674.2:g.102852941C>A

NC_000012.11:g.103246719C>A

CM000674.1:g.103246719C>A

NC_000012.10:g.101770849C>A

NG_008690.1:g.69662G>T

NG_008690.2:g.110470G>T

NM_000277.2:c.716G>T

NM_001354304.1:c.716G>T

NM_000277.3:c.716G>T

NM_001354304.2:c.716G>T

ENST00000307000.7:c.701G>T

ENST00000549247.6:n.475G>T

ENST00000553106.5:c.716G>T

Likely Pathogenic

PP4 PP3 PM2 PM3

PM5

Evidence Links 3

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.716G>T (p.Gly239Val) variant in PAH has been reported in 2 individuals with classic PKU (PMID 10394930, 31623983) detected with pathogenic variants p.R408W and IVS10–11g>a (PMID: 32106880). This variant has extremely low frequency in gnomAD (MAF=0.00006). 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.

PP4

PMID 10394930: In Table 1, listed on allele of p.Gly239Val in a cohort of Germany PKU/HPA patients. PMID: 31623983 Detected in a classic PKU patient at Boston Children's. BH4 deficiency not reportedly ruled out PMID: 32106880

In Table 1, listed on allele of p.Gly239Val in a cohort of Germany PKU/HPA patients. PubMed:10394930

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.978

PM2

extremely low frequency in GnomAD (MAF=0.00006)

PM3

detected with p.R408W (P 14 submitters) PMID: 31623983 IVS10–11g>a (P 7 submitters) PMID: 32106880 parental analysis not reported

PubMed:31623983

PubMed:32106880

PM5

p.Gly239Ala/Ser/Asp no interpretation in ClinVar

Approved on: 2020-10-23

Published on: 2020-10-23

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