NM_000277.3(PAH):c.60+62C>T AND Phenylketonuria

Germline classification:: Benign (5 submissions)
Last evaluated:: Nov 8, 2019
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000709703.5

Allele description [Variation Report for NM_000277.3(PAH):c.60+62C>T]

NM_000277.3(PAH):c.60+62C>T

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.60+62C>T

HGVS:

NC_000012.12:g.102917009G>A
NG_008690.2:g.46402C>T
NM_000277.2(PAH):c.60+62C>T
NM_000277.3:c.60+62C>TMANE SELECT
NM_001354304.2:c.60+62C>T
NC_000012.11:g.103310787G>A
NM_000277.1:c.60+62C>T
NM_000277.2(PAH):c.60+62C>T
NM_000277.2:c.60+62C>T

Links:

dbSNP: rs1522296

NCBI 1000 Genomes Browser:

rs1522296

Molecular consequence:

NM_000277.3:c.60+62C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001354304.2:c.60+62C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Phenylketonuria (PKU)
Synonyms:: FOLLING DISEASE; OLIGOPHRENIA PHENYLPYRUVICA; Phenylketonurias
Identifiers:: MONDO: MONDO:0009861; MedGen: C0031485; Orphanet: 716; OMIM: 261600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000839874	Clinical Laboratory, Xuzhou Maternity and Child Health Care Hospital	no assertion criteria provided	Likely pathogenic (Jun 26, 2018)	inherited	case-control
SCV001142436	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Benign (Jan 6, 2020)	germline	curation
SCV001250539	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Benign (Nov 8, 2019)	germline	curation	Citation Link,
SCV001750014	Pars Genome Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004812732	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
Chinese Han	inherited	unknown	6	not provided	not provided	not provided	not provided	case-control

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Clinical Laboratory, Xuzhou Maternity and Child Health Care Hospital, SCV000839874.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Chinese Han	6	not provided	not provided	case-control	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	unknown	not provided	not provided	not provided		6	not provided	not provided	not provided

From Reproductive Health Research and Development, BGI Genomics, SCV001142436.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

NG_008690.2(NM_000277.2):c.60+62C>T in the gene PAH has an allele frequency of 0.496 in African subpopulation in the gnomAD database. A total of 2014 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen PAH Variant Curation Expert Panel, SCV001250539.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.60+62C>T intronic variant in PAH has a MAF of 0.3441 in gnomAD with 2,014 homozygotes.In summary, this variant meets criteria to be classified as benign for PAH. PAH-specific ACMG/AMP criteria applied: BA1, BS2, BP7.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Pars Genome Lab, SCV001750014.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Genetics, Royal Melbourne Hospital, SCV004812732.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

African/African American population allele frequency is 48.34% (rs1522296, 4299/8672 alleles, 1055 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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