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.441+47C>T

CA229547

102673 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5eaf5d22-71c9-4189-b409-34f76d3ca843

HGVS expressions

NM_000277.3:c.441+47C>T

NM_000277.3(PAH):c.441+47C>T

NC_000012.12:g.102877415G>A

CM000674.2:g.102877415G>A

NC_000012.11:g.103271193G>A

CM000674.1:g.103271193G>A

NC_000012.10:g.101795323G>A

NG_008690.1:g.45188C>T

NG_008690.2:g.85996C>T

ENST00000553106.6:c.441+47C>T

ENST00000307000.7:c.426+47C>T

ENST00000549111.5:n.537+47C>T

ENST00000550978.6:n.472C>T

ENST00000551988.5:n.530+47C>T

ENST00000553106.5:c.441+47C>T

NM_000277.1:c.441+47C>T

NM_000277.2:c.441+47C>T

NM_001354304.1:c.441+47C>T

NM_001354304.2:c.441+47C>T

Benign

BA1 BP7

PP4 PM3 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.441+47C>T variant in PAH is widely found in population databases at a frequency of 0.372401 in ExAC. This intronic variant is not predicted to have a splice-altering consequence. In summary, this variant meets criteria to be classified as a benign for PAH. PAH-specific ACMG/AMP criteria applied: BP7, BA1.

BA1

Present in European population at frequency of 0.4394 and in all populations at frequency of 0.294329 (1000 genomes). Present in European Non-Finnish population at frequency of 0.430887 and in all populations at frequency of 0.372401(ExAC). T

BP7

This is an intronic variant which is not located in a splice region and not predicted to have a splice-altering consequence. Several insilico prediction tools did not have a classification score for this variant (SpliceA, dbscSNV, Ada and RF score). This variant was classified as benign according to TraP (score =0.063).

PP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

Present in European Non-Finnish population at frequency of 0.450036 and in all populations at frequency of 0.39109 (gnomAD). Present in European Non-Finnish population at frequency of 0.430887 and in all populations at frequency of 0.372401(ExAC). The PM2 threshold set by the PAH Variant Curation Expert Panel (VCEP) is 0.0002

Approved on: 2022-12-09

Published on: 2022-12-09

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