NM_000277.3(PAH):c.124_126del (p.Lys42del) AND Phenylketonuria

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Oct 16, 2020
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:: RCV000667507.3

Allele description [Variation Report for NM_000277.3(PAH):c.124_126del (p.Lys42del)]

NM_000277.3(PAH):c.124_126del (p.Lys42del)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.124_126del (p.Lys42del)

HGVS:

NC_000012.12:g.102912833_102912835del
NG_008690.2:g.50576_50578del
NM_000277.3:c.124_126delMANE SELECT
NM_001354304.2:c.124_126del
NP_000268.1:p.Lys42del
NP_001341233.1:p.Lys42del
NC_000012.11:g.103306611_103306613del
NM_000277.1:c.124_126delAAA

Protein change:

K42del

Links:

dbSNP: rs1555209578

NCBI 1000 Genomes Browser:

rs1555209578

Molecular consequence:

NM_000277.3:c.124_126del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354304.2:c.124_126del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000791969	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jun 1, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001448284	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Likely pathogenic (Oct 16, 2020)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 30050108, 27243974 Citation Link,
SCV004201961	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 14, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000791969

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jun 1, 2017)

unknown

clinical testing

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

Citation Link,

SCV001448284

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Likely pathogenic
(Oct 16, 2020)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV004201961

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 14, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of the genotype-phenotype correlation in patients with phenylketonuria in mainland China.

Li N, He C, Li J, Tao J, Liu Z, Zhang C, Yuan Y, Jiang H, Zhu J, Deng Y, Guo Y, Li Q, Yu P, Wang Y.

Sci Rep. 2018 Jul 26;8(1):11251. doi: 10.1038/s41598-018-29640-y.

PubMed [citation]

PMID:: 30050108
PMCID:: PMC6062512

Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism.

Yubero D, Brandi N, Ormazabal A, Garcia-Cazorla À, Pérez-Dueñas B, Campistol J, Ribes A, Palau F, Artuch R, Armstrong J; Working Group..

PLoS One. 2016;11(5):e0156359. doi: 10.1371/journal.pone.0156359.

PubMed [citation]

PMID:: 27243974
PMCID:: PMC4887012

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000791969.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen PAH Variant Curation Expert Panel, SCV001448284.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

The c.124_126del (p.Lys42del) PAH variant has been reported in 2 patients with PAH deficiency, detected with the pathogenic PAH variant p.Arg111Ter (PMID: 30050108) and the likely pathogenic PAH variant c.824C>T (PMID: 27243974). A defect in BH4 metabolism was not excluded. This variant is absent from population databases. The protein length changes as a result of an in-frame deletion in a non-repeat region. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3_strong, PM4, PP4.

#	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 Baylor Genetics, SCV004201961.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 30, 2023

ClinVar

Relating variation to medicine