NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter) AND Peroxisome biogenesis disorders, Zellweger syndrome spectrum

Clinical significance:Likely pathogenic (Last evaluated: Nov 18, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000590014.1

Allele description [Variation Report for NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter)]

NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter)

Genes:
GATAD1:GATA zinc finger domain containing 1 [Gene - OMIM - HGNC]
PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.2
Genomic location:
Preferred name:
NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter)
HGVS:
  • NC_000007.14:g.92494331G>A
  • NG_008341.1:g.39201C>T
  • NG_008341.2:g.39201C>T
  • NM_000466.3:c.2992C>TMANE SELECT
  • NM_001282677.2:c.2821C>T
  • NM_001282678.2:c.2368C>T
  • NP_000457.1:p.Arg998Ter
  • NP_001269606.1:p.Arg941Ter
  • NP_001269607.1:p.Arg790Ter
  • NC_000007.13:g.92123645G>A
  • NM_000466.2:c.2992C>T
Protein change:
R790*
Links:
dbSNP: rs61750428
NCBI 1000 Genomes Browser:
rs61750428
Molecular consequence:
  • NM_000466.3:c.2992C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001282677.2:c.2821C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001282678.2:c.2368C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Peroxisome biogenesis disorders, Zellweger syndrome spectrum (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:
MedGen: C1832200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696796Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Nov 18, 2016)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ.

Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.

PubMed [citation]
PMID:
25525159
PMCID:
PMC4362528

Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.

Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG.

Hum Mutat. 2009 Mar;30(3):E467-80. doi: 10.1002/humu.20932.

PubMed [citation]
PMID:
19105186
PMCID:
PMC2649967

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696796.1

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

Description

Variant summary: The PEX1 c.2992C>T (p.Arg998X) variant results in a premature termination codon, predicted to cause a truncated or absent PEX1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A functional assay using patient cells showed that this variant leads significant reduction in synthesis of mRNA (Maxwell_2002). Truncations downstream of this position have been classified as pathogenic by laboratories in ClinVar (e.g. c.3505_3517delCAGTTGTTTTCAC, c.3693_3696delGTCA, p.Trp1250Ter, etc.). This variant was found in 1/119888 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX1 variant (0.003873). This variant has been reported in two patients with a confirmed dx of Zellweger syndrome. Taken together, this variant is classified as Likely Pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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