NM_000466.3(PEX1):c.2240A>C (p.Glu747Ala) AND Zellweger spectrum disorders

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 16, 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:: RCV001832433.12

Allele description [Variation Report for NM_000466.3(PEX1):c.2240A>C (p.Glu747Ala)]

NM_000466.3(PEX1):c.2240A>C (p.Glu747Ala)

Gene:

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.2240A>C (p.Glu747Ala)

HGVS:

NC_000007.14:g.92502066T>G
NG_008341.2:g.31466A>C
NM_000466.3:c.2240A>CMANE SELECT
NM_001282677.2:c.2069A>C
NM_001282678.2:c.1616A>C
NP_000457.1:p.Glu747Ala
NP_001269606.1:p.Glu690Ala
NP_001269607.1:p.Glu539Ala
NC_000007.13:g.92131380T>G
NC_000007.13:g.92131380T>G
NG_008341.1:g.31466A>C
NM_000466.2:c.2240A>C

Protein change:

E539A

Links:

dbSNP: rs200207576

NCBI 1000 Genomes Browser:

rs200207576

Molecular consequence:

NM_000466.3:c.2240A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282677.2:c.2069A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282678.2:c.1616A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Zellweger spectrum disorders (ZS)
Synonyms:: Zellweger syndrome; Zellweger Spectrum Disorder; Zellweger Spectrum
Identifiers:: MONDO: MONDO:0019609; MedGen: C0043459; Orphanet: 912

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001209228	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002076871	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 29, 2018)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001209228

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002076871

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 29, 2018)

germline

clinical testing

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001209228.3

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 747 of the PEX1 protein (p.Glu747Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 842882). 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

From Natera, Inc., SCV002076871.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine