NM_000466.3(PEX1):c.2873_2875delinsT (p.Asp958fs) AND Heimler syndrome 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jul 5, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003473893.2

Allele description [Variation Report for NM_000466.3(PEX1):c.2873_2875delinsT (p.Asp958fs)]

NM_000466.3(PEX1):c.2873_2875delinsT (p.Asp958fs)

Genes:

GATAD1:GATA zinc finger domain containing 1 [Gene - OMIM - HGNC]
PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

7q21.2

Genomic location:

Preferred name:

NM_000466.3(PEX1):c.2873_2875delinsT (p.Asp958fs)

HGVS:

NC_000007.14:g.92494538_92494540delinsA
NG_008341.2:g.38992_38994delinsT
NM_000466.3:c.2873_2875delinsTMANE SELECT
NM_001282677.2:c.2702_2704delinsT
NM_001282678.2:c.2249_2251delinsT
NP_000457.1:p.Asp958fs
NP_001269606.1:p.Asp901fs
NP_001269607.1:p.Asp750fs
NC_000007.13:g.92123852_92123854delinsA
NM_000466.3:c.2873_2875delACCinsTMANE SELECT

Protein change:

D750fs

Links:

dbSNP: rs2116094537

NCBI 1000 Genomes Browser:

rs2116094537

Molecular consequence:

NM_000466.3:c.2873_2875delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282677.2:c.2702_2704delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282678.2:c.2249_2251delinsT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Heimler syndrome 1 (HMLR1)
Synonyms:: PEROXISOME BIOGENESIS DISORDER 1C
Identifiers:: MedGen: C4551980; Orphanet: 3220; OMIM: 234580

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004203286	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 19, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005203652	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jul 5, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004203286

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 19, 2023)

unknown

clinical testing

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

SCV005203652

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jul 5, 2024)

germline

clinical testing

Citation Link

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Baylor Genetics, SCV004203286.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005203652.1

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

Description

Variant summary: PEX1 c.2873_2875delinsT (p.Asp958ValfsX4) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 4e-06 in 251342 control chromosomes. To our knowledge, no occurrence of c.2873_2875delinsT in individuals affected with Heimler Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1065420). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine