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NM_000287.4(PEX6):c.2482C>T (p.Gln828Ter) AND Peroxisome biogenesis disorder 4A (Zellweger)

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 4, 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:
RCV002277753.2

Allele description [Variation Report for NM_000287.4(PEX6):c.2482C>T (p.Gln828Ter)]

NM_000287.4(PEX6):c.2482C>T (p.Gln828Ter)

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.2482C>T (p.Gln828Ter)
HGVS:
  • NC_000006.12:g.42965358G>A
  • NG_008370.1:g.18886C>T
  • NG_008396.1:g.9597G>A
  • NM_000287.4:c.2482C>TMANE SELECT
  • NM_001316313.2:c.2218C>T
  • NP_000278.3:p.Gln828Ter
  • NP_001303242.1:p.Gln740Ter
  • NC_000006.11:g.42933096G>A
  • NR_133009.2:n.2266C>T
Protein change:
Q740*
Links:
dbSNP: rs267608243
NCBI 1000 Genomes Browser:
rs267608243
Molecular consequence:
  • NR_133009.2:n.2266C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000287.4:c.2482C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001316313.2:c.2218C>T - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
RNA degradation by nonsense-mediated decay [Variation Ontology: 0347]
Observations:
1

Condition(s)

Name:
Peroxisome biogenesis disorder 4A (Zellweger) (PBD4A)
Synonyms:
Zellweger syndrome spectrum (PEX6-related)
Identifiers:
MONDO: MONDO:0013930; MedGen: C3553936; Orphanet: 912; OMIM: 614862

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002558699Centre de Genetique Humaine, Institut de Pathologie et de Genetique
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jul 4, 2022) 		maternal, not applicableclinical testing, in vitro

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providednot applicablenot applicablenot providednot providednot providednot providednot providedin vitro
Causasianmaternalyes1not providednot providednot providednot providedclinical 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

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 Centre de Genetique Humaine, Institut de Pathologie et de Genetique, SCV002558699.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedin vitro PubMed (2)
2Causasian1not providednot providedclinical testing PubMed (2)

Description

Clinical & biochemical phenotypes compatible with Zellweger spectrum disorder diagnosis & genotype.

Description

Nonsense variant in a gene where LOF is a known mechanism of disease. Not present in GnomAD. Reported in PMID: 19877282 in heterozygous state in a patient with ZSD. This variant is targeted by nonsense-mediated mRNA decay (NMD) as shown by RNA analysis on patient's skin fibroblast. Inherited from the patient's mother. The patient is compound heterozygous for this variant and c.929C>T p.(Ser310Leu) in PEX6 gene (see this variant for more information). Patient's biochemical profile: ON PLASMA SAMPLE: - VLCFA: C26:0 is elevated, C26/C22 ratio is elevated - Phytanic acid: elevated - Pristanic acid: elevated - Pipecolic acid: 40x the upper limit of the normal ON URINE SAMPLE: - Organic acid profile: epoxy-dicarboxylic derivatives, 2-hydroxy-sébacate, 3-hydroxy-sebacate, pimelate and azelaate, compatible with PBD ON RED BLOOD CELL SAMPLE: - Plasmalogens: C16:0 DMA/C16:0 is decreased Patient's biochemical profile: ON PLASMA SAMPLE: - VLCFA: C26:0 is elevated, C26/C22 ratio is elevated - Phytanic acid: elevated - Pristanic acid: elevated - Pipecolic acid: 40x the upper limit of the normal ON URINE SAMPLE: - Organic acid profile: epoxy-dicarboxylic derivatives, 2-hydroxy-sébacate, 3-hydroxy-sebacate, pimelate and azelaate, compatible with PBD ON RED BLOOD CELL SAMPLE: - Plasmalogens: C16:0 DMA/C16:0 is decreased ON SKIN FIBROBLASTS : - Catalase IF showed import deficiency at 37°C (partially restored at 30°C) - 16:0_22:6GEtn : decreased levels - 16:0_20:6GEtn : decreased levels

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not applicablenot applicablenot providedSkinnot providednot providednot providednot providednot provided
2maternalyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Jun 23, 2024