U.S. flag

An official website of the United States government

NM_000277.3(PAH):c.60+9C>T AND Phenylketonuria

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Jul 23, 2023
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:
RCV001279869.9

Allele description [Variation Report for NM_000277.3(PAH):c.60+9C>T]

NM_000277.3(PAH):c.60+9C>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+9C>T
HGVS:
  • NC_000012.12:g.102917062G>A
  • NG_008690.2:g.46349C>T
  • NM_000277.3:c.60+9C>TMANE SELECT
  • NM_001354304.2:c.60+9C>T
  • NC_000012.11:g.103310840G>A
Links:
dbSNP: rs369454152
NCBI 1000 Genomes Browser:
rs369454152
Molecular consequence:
  • NM_000277.3:c.60+9C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354304.2:c.60+9C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Phenylketonuria (PKU)
Synonyms:
Phenylketonurias; Oligophrenia phenylpyruvica; Folling disease
Identifiers:
MONDO: MONDO:0009861; MedGen: C0031485; Orphanet: 716; OMIM: 261600

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001467003Natera, Inc.
no assertion criteria provided
Uncertain significance
(Apr 17, 2020)
germlineclinical testing

SCV001676517Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(Dec 20, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004015322ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)
Uncertain significance
(Jul 23, 2023)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Natera, Inc., SCV001467003.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001676517.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen PAH Variant Curation Expert Panel, SCV004015322.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000277.3:c.60+9C>T variant in PAH is an intronic variant affecting a nucleotide in intron 1. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0002803 (7/24972 alleles) in the African/African American population (none of the population data codes are met). The computational splicing predictor SpliceAI gives a score of 0.01 for donor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 991626, 1 star review status) with one submitter classifying the variant as a variant of uncertain significance and one submitter classifying the variant as likely benign. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH Variant Curation Expert Panel (Specifications Version 2.0): BP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024