NM_000287.4(PEX6):c.1992G>C (p.Glu664Asp) AND Peroxisome biogenesis disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 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:: RCV001248070.6

Allele description [Variation Report for NM_000287.4(PEX6):c.1992G>C (p.Glu664Asp)]

NM_000287.4(PEX6):c.1992G>C (p.Glu664Asp)

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.1992G>C (p.Glu664Asp)

HGVS:

NC_000006.12:g.42966627C>G
NG_008370.1:g.17617G>C
NM_000287.4:c.1992G>CMANE SELECT
NM_001316313.2:c.1728G>C
NP_000278.3:p.Glu664Asp
NP_001303242.1:p.Glu576Asp
NC_000006.11:g.42934365C>G
NC_000006.11:g.42934365C>G
NM_000287.3:c.1992G>C
NR_133009.2:n.2023G>C

Protein change:

E576D

Links:

dbSNP: rs267608230

NCBI 1000 Genomes Browser:

rs267608230

Molecular consequence:

NM_000287.4:c.1992G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001316313.2:c.1728G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_133009.2:n.2023G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Epithalamus
Epithalamus
The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (HABENULA) and associated fiber bundles, the PINE...<br/>Year introduced: 1997

MeSH
White Matter
White Matter
The region of CENTRAL NERVOUS SYSTEM that appears lighter in color than the other type, GRAY MATTER. It mainly consists of MYELINATED NERVE FIBERS and contains few neuronal ce...<br/>Year introduced: 2015

MeSH
Gray Matter
Gray Matter
Region of CENTRAL NERVOUS SYSTEM that appears darker in color than the other type, WHITE MATTER. It is composed of neuronal CELL BODIES; NEUROPIL; GLIAL CELLS and CAPILLARIES ...<br/>Year introduced: 2015

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421535	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19877282, 26287655, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001421535

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients.

Ebberink MS, Kofster J, Wanders RJ, Waterham HR.

Hum Mutat. 2010 Jan;31(1):E1058-70. doi: 10.1002/humu.21153.

PubMed [citation]

PMID:: 19877282

Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood.

Berendse K, Engelen M, Ferdinandusse S, Majoie CB, Waterham HR, Vaz FM, Koelman JH, Barth PG, Wanders RJ, Poll-The BT.

J Inherit Metab Dis. 2016 Jan;39(1):93-106. doi: 10.1007/s10545-015-9880-2. Epub 2015 Aug 19.

PubMed [citation]

PMID:: 26287655
PMCID:: PMC4710674

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001421535.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 664 of the PEX6 protein (p.Glu664Asp). This variant is present in population databases (rs267608230, gnomAD 0.02%). This missense change has been observed in individual(s) with Zellweger Syndrome Spectrum (PMID: 19877282, 26287655). ClinVar contains an entry for this variant (Variation ID: 972112). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

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