NM_002617.4(PEX10):c.600+1G>A AND Peroxisome biogenesis disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001174563.2

Allele description [Variation Report for NM_002617.4(PEX10):c.600+1G>A]

NM_002617.4(PEX10):c.600+1G>A

Gene:

PEX10:peroxisomal biogenesis factor 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.32

Genomic location:

Preferred name:

NM_002617.4(PEX10):c.600+1G>A

HGVS:

NC_000001.11:g.2408451C>T
NG_008342.1:g.9121G>A
NM_001374425.1:c.600+1G>A
NM_001374426.1:c.168+1G>A
NM_001374427.1:c.168+1G>A
NM_002617.4:c.600+1G>AMANE SELECT
NM_153818.2:c.600+1G>A
NC_000001.10:g.2339890C>T
NM_002617.3:c.600+1G>A
NM_153818.1:c.600+1G>A

Note:

NCBI staff reviewed the sequence information reported in PubMed 9683594 to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS, G-A, +1

Links:

OMIM: 602859.0001; dbSNP: rs267608183

NCBI 1000 Genomes Browser:

rs267608183

Molecular consequence:

NM_001374425.1:c.600+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001374426.1:c.168+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001374427.1:c.168+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_002617.4:c.600+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_153818.2:c.600+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Peroxisome biogenesis disorder (PBD, ZSS)
Synonyms:: PEROXISOME BIOGENESIS DISORDER (NEONATAL ADRENOLEUKODYSTROPHY/INFANTILE REFSUM DISEASE); INFANTILE PHYTANIC ACID STORAGE DISEASE; PEROXISOME BIOGENESIS DISORDER (NALD/IRD); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019234; MedGen: C1832200; OMIM: PS214100

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
SCV001337725	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21031596, 19127411, 9683594, 30640048 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001337725

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 9, 2022)

germline

clinical testing

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

Citation Link

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

Citations

PubMed

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.

Ebberink MS, Mooijer PA, Gootjes J, Koster J, Wanders RJ, Waterham HR.

Hum Mutat. 2011 Jan;32(1):59-69. doi: 10.1002/humu.21388.

PubMed [citation]

PMID:: 21031596

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts.

Steinberg SJ, Snowden A, Braverman NE, Chen L, Watkins PA, Clayton PT, Setchell KD, Heubi JE, Raymond GV, Moser AB, Moser HW.

J Inherit Metab Dis. 2009 Feb;32(1):109-19. doi: 10.1007/s10545-008-0969-8. Epub 2008 Dec 25.

PubMed [citation]

PMID:: 19127411

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337725.2

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

Description

Variant summary: PEX10 c.600+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict that the variant abolishes a 5 prime splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Warren_1998). The variant allele was found at a frequency of 2.4e-05 in 248440 control chromosomes (gnomAD). c.600+1G>A has been reported in the literature in at least one individual affected with Zellweger Syndrome (Warren_1998, homozygous mutation) . These data indicate that the variant may be associated with disease. Sveral publications report experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Warren_1998, Steinberg_2009). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine