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NM_000466.3(PEX1):c.3665C>T (p.Pro1222Leu) AND Zellweger spectrum disorders

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 27, 2021
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:
RCV001987958.4

Allele description [Variation Report for NM_000466.3(PEX1):c.3665C>T (p.Pro1222Leu)]

NM_000466.3(PEX1):c.3665C>T (p.Pro1222Leu)

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.3665C>T (p.Pro1222Leu)
HGVS:
  • NC_000007.14:g.92489395G>A
  • NG_008341.2:g.44137C>T
  • NM_000466.3:c.3665C>TMANE SELECT
  • NM_001282677.2:c.3494C>T
  • NM_001282678.2:c.3041C>T
  • NP_000457.1:p.Pro1222Leu
  • NP_001269606.1:p.Pro1165Leu
  • NP_001269607.1:p.Pro1014Leu
  • NC_000007.13:g.92118709G>A
Protein change:
P1014L
Links:
dbSNP: rs371575516
NCBI 1000 Genomes Browser:
rs371575516
Molecular consequence:
  • NM_000466.3:c.3665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282677.2:c.3494C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282678.2:c.3041C>T - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002225043Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 27, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV002225043.2

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

Description

This sequence change replaces proline with leucine at codon 1222 of the PEX1 protein (p.Pro1222Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs371575516, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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

Last Updated: Dec 24, 2023