VCV000631556.1 - ClinVar

NM_003630.3(PEX3):c.942-8T>G

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003630.3(PEX3):c.942-8T>G

Variation ID: 631556 Accession: VCV000631556.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6q24.2 6: 143485144 (GRCh38) [ NCBI UCSC ] 6: 143806281 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 17, 2017	May 27, 2019	May 23, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_003630.3:c.942-8T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000006.12:g.143485144T>G
NC_000006.11:g.143806281T>G
NG_008459.1:g.39364T>G

Protein change

Other names

IVS10AS, T-G, -8

Canonical SPDI

NC_000006.12:143485143:T:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 603164.0002 dbSNP: rs267608193 VarSome

Comment on variant

ClinGen staff contributed the HGVS expression for this variant.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PEX3		-	-	GRCh38 GRCh37	380	395

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Peroxisome biogenesis disorder 10A (Zellweger)	Pathogenic (1)	no assertion criteria provided	Oct 1, 2000	RCV000006998.3
Peroxisome biogenesis disorder 1A (Zellweger)	Pathogenic (1)	criteria provided, single submitter	May 23, 2019	RCV000778169.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 23, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Zellweger syndrome (Autosomal recessive inheritance) Affected status: no Allele origin: germline	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital Accession: SCV000914248.1 First in ClinVar: May 27, 2019 Last updated: May 27, 2019
Pathogenic (Oct 01, 2000)	no assertion criteria provided Method: literature only	PEROXISOME BIOGENESIS DISORDER 10A (ZELLWEGER) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000027194.2 First in ClinVar: Apr 04, 2013 Last updated: Feb 17, 2017	Publications: PubMed (3) PubMed: 10958759‚ 10968777‚ 7562283 Comment on evidence: In a patient (patient 2, PBDG-02) with Zellweger syndrome of complementation group G (PBD10A; 614882), Muntau et al. (2000) found a T-to-G transversion at position … (more) In a patient (patient 2, PBDG-02) with Zellweger syndrome of complementation group G (PBD10A; 614882), Muntau et al. (2000) found a T-to-G transversion at position -8 of the 3-prime acceptor splice site of intron 10 of the PEX3 gene. This mutation led to deletion of exon 11 and a frameshift, with a premature termination after 3 amino acids, predicting a 56-amino acid C-terminal truncation of the protein. The male infant was cyanotic and markedly hypotonic at birth with absent deep tendon reflexes. He had a prominent midface and downslanting palpebral fissures, ocular hypertelorism, small low-set ears, a prominent nose, and a high-arched palate. The patient died at age 19 days. A brother had been similarly affected and died at age 15 days. Ghaedi et al. (2000) demonstrated the same mutation in a study of material from the same patient. Poulos et al. (1995) originally studied this patient (patient 2) and described clinical, pathologic, and biochemical findings. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G.	Ghaedi K	American journal of human genetics	2000	PMID: 10968777
Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G.	Muntau AC	American journal of human genetics	2000	PMID: 10958759
Peroxisomal assembly defects: clinical, pathologic, and biochemical findings in two patients in a newly identified complementation group.	Poulos A	The Journal of pediatrics	1995	PMID: 7562283

Text-mined citations for rs267608193 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_003630.3(PEX3):c.942-8T>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs267608193 ...