VCV000008126.3 - ClinVar

NM_000287.4(PEX6):c.2094G>A (p.Lys698=)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000287.4(PEX6):c.2094G>A (p.Lys698=)

Variation ID: 8126 Accession: VCV000008126.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.1 6: 42966525 (GRCh38) [ NCBI UCSC ] 6: 42934263 (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	Sep 21, 2016	Apr 6, 2024	Mar 17, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000287.4:c.2094G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000278.3:p.Lys698=	synonymous
NM_001316313.2:c.1830G>A	NP_001303242.1:p.Lys610=	synonymous
NR_133009.2:n.2125G>A		non-coding transcript variant
NC_000006.12:g.42966525C>T
NC_000006.11:g.42934263C>T
NG_008370.1:g.17719G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000006.12:42966524:C:T

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: 601498.0008 VarSome

Comment on variant

NCBI staff provided an HGVS expression for allelic variant 601498.0008 based on the statement that the altered splicing resulted from '..point mutation, G>A, at the 39-terminus of exon 12. The sequence at the end of that exon was reported as CCCCAAG. (Matsumoto et al. 2001, PubMed 11355018).

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.
PEX6		-	-	GRCh38 GRCh37	1759	1779

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 4B	Uncertain significance (2)	criteria provided, single submitter	Mar 17, 2024	RCV000008599.9

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.
Uncertain significance (Mar 17, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Peroxisome biogenesis disorder 4B Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004804983.2 First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024
Pathogenic (Jan 01, 2001)	no assertion criteria provided Method: literature only	PEROXISOME BIOGENESIS DISORDER 4B Affected status: not provided Allele origin: germline	OMIM Accession: SCV000028807.4 First in ClinVar: Apr 04, 2013 Last updated: Sep 21, 2016	Publications: PubMed (1) PubMed: 11355018 Comment on evidence: For discussion of the deletion of nucleotides 2095-2362 along with an insertion of 21 nucleotides in the PEX6 gene that was found in compound heterozygous … (more) For discussion of the deletion of nucleotides 2095-2362 along with an insertion of 21 nucleotides in the PEX6 gene that was found in compound heterozygous state in a patient with a diagnosis of neonatal adrenoleukodystrophy (NALD) belonging to complementation group 6 of the peroxisome biogenesis disorders (PBD4B; 614863) by Matsumoto et al. (2001), see 601498.0007. (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
The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6.	Matsumoto N	Journal of human genetics	2001	PMID: 11355018

Text-mined citations for this variant ...

Record last updated Aug 04, 2024

ClinVar Genomic variation as it relates to human health

NM_000287.4(PEX6):c.2094G>A (p.Lys698=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...