NM_001127649.3(PEX26):c.134T>C (p.Leu45Pro) AND Peroxisome biogenesis disorder 7A (Zellweger)

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 30, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000351940.7

Allele description [Variation Report for NM_001127649.3(PEX26):c.134T>C (p.Leu45Pro)]

NM_001127649.3(PEX26):c.134T>C (p.Leu45Pro)

Gene:

PEX26:peroxisomal biogenesis factor 26 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_001127649.3(PEX26):c.134T>C (p.Leu45Pro)

HGVS:

NC_000022.11:g.18078510T>C
NG_008339.1:g.5591T>C
NM_001127649.3:c.134T>CMANE SELECT
NM_001199319.2:c.134T>C
NM_017929.6:c.134T>C
NP_001121121.1:p.Leu45Pro
NP_001186248.1:p.Leu45Pro
NP_060399.1:p.Leu45Pro
NC_000022.10:g.18561276T>C
NM_017929.5:c.134T>C
Q7Z412:p.Leu45Pro

Protein change:

L45P; LEU45PRO

Links:

UniProtKB: Q7Z412#VAR_018647; OMIM: 608666.0006; dbSNP: rs61752132

NCBI 1000 Genomes Browser:

rs61752132

Molecular consequence:

NM_001127649.3:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001199319.2:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_017929.6:c.134T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Peroxisome biogenesis disorder 7A (Zellweger)
Synonyms:: Peroxisome biogenesis disorder 7A
Identifiers:: MONDO: MONDO:0013938; MedGen: C3888385; Orphanet: 912; OMIM: 614872

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000437325	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12851857, 15858711, 25016021, 16257970 Citation Link,
SCV004201496	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 30, 2023)	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

SCV000437325

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV004201496

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 30, 2023)

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	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation.

Matsumoto N, Tamura S, Furuki S, Miyata N, Moser A, Shimozawa N, Moser HW, Suzuki Y, Kondo N, Fujiki Y.

Am J Hum Genet. 2003 Aug;73(2):233-46. Epub 2003 Jul 8.

PubMed [citation]

PMID:: 12851857
PMCID:: PMC1180364

Alternative splicing suggests extended function of PEX26 in peroxisome biogenesis.

Weller S, Cajigas I, Morrell J, Obie C, Steel G, Gould SJ, Valle D.

Am J Hum Genet. 2005 Jun;76(6):987-1007. Epub 2005 Apr 27.

PubMed [citation]

PMID:: 15858711
PMCID:: PMC1196456

See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000437325.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The PEX26 c.134T>C (p.Leu45Pro) missense variant was reported in a compound heterozygous state with a second missense variant in one individual with infantile Refsum disease, which is part of the Zellweger spectrum (Matsumoto et al. 2003). Control data are not available and allele frequency information for this variant is not reported in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Expression of the p.Leu45Pro variant in a PEX26-deficient CHO cell line showed that the variant did not restore impaired peroxisome biogenesis (Matsumoto et al. 2003, Weller et al. 2005) and interfered with interactions with other PEX proteins (Furuki et al. 2006; Tamura et al. 2014). Based on the evidence, the p.Leu45Pro variant is classified as a variant of unknown significance but suspicious for pathogenicity for Zellweger syndrome spectrum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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, SCV004201496.1

#	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: Sep 29, 2024

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