NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) AND PEX6-related disorder

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Nov 19, 2019
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:: RCV001265584.5

Allele description [Variation Report for NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln)]

NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln)

Gene:

PEX6:peroxisomal biogenesis factor 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln)

HGVS:

NC_000006.12:g.42967450C>T
NG_008370.1:g.16794G>A
NM_000287.4:c.1802G>AMANE SELECT
NM_001316313.2:c.1538G>A
NP_000278.3:p.Arg601Gln
NP_001303242.1:p.Arg513Gln
NC_000006.11:g.42935188C>T
NM_000287.3:c.1802G>A
NM_001316313.1:c.1538G>A
NR_133009.2:n.1833G>A
Q13608:p.Arg601Gln

Protein change:

R513Q; ARG601GLN

Links:

UniProtKB: Q13608#VAR_058383; OMIM: 601498.0012; dbSNP: rs34324426

Molecular consequence:

NM_000287.4:c.1802G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001316313.2:c.1538G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_133009.2:n.1833G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: PEX6-related disorder
Synonyms:: PEX6-Related Disorders; PEX6-related condition
Identifiers:

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
SCV001443749	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 19, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004107814	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Uncertain significance (Jul 18, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001443749

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 19, 2019)

germline

clinical testing

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

SCV004107814

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Uncertain significance
(Jul 18, 2024)

germline

clinical testing

Help

Summary from all submissions

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

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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001443749.1

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

Description

This variant has been previously reported as a compound heterozygous change with multiple different variants, including c.2579G>A (p.Arg860Gln), in patients with peroxisome biogenesis disorder (Zellweger syndrome) or Heimler Syndrome, including bilateral sensorineural hearing loss, amelogenesis imperfecta, nail abnormalities, and retinal pigmentation (PMID: 19105186, 26387595, 27302843). Functional studies of this variant demonstrate that it has significant residual activity, suggesting that it may be a hypomorphic allele (PMID: 26387595). Haplotype analysis of this variant show that it is consistently associated with a haplotype of two SNPs and a 779 KB microsatellite, suggesting that this variant is a founder variant that may have arisen many generations ago (PMID: 27302843). In the gnomAD population database, it is present in the homozygous state in 7 individuals and it is present in the heterozygous state at a frequency of 0.30% (821/277,712). The c.1802G>A (p.Arg601Gln) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.1802G>A (p.Arg601Gln) variant is classified as Likely Pathogenic.

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

From PreventionGenetics, part of Exact Sciences, SCV004107814.3

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

Description

The PEX6 c.1802G>A variant is predicted to result in the amino acid substitution p.Arg601Gln. This variant has been reported in patients with peroxisome biogenesis disorders and has been reported to be associated with a milder phenotype (Ebberink et al. 2010. PubMed ID: 19877282; Yik et al. 2009. PubMed ID: 19105186; Ratbi et al. 2015. PubMed ID: 26387595; Wangtiraumnuay et al. 2018; PubMed ID: 29676688). However, this variant has also been reported in a large population database at allele frequencies of up to ~0.47%, including 7 homozygous individuals. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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: Jun 20, 2026

ClinVar

Relating variation to medicine