NM_002085.5(GPX4):c.438_441del (p.Lys145_Trp146insTer) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 13, 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:: RCV001919596.3

Allele description

NM_002085.5(GPX4):c.438_441del (p.Lys145_Trp146insTer)

Gene:

GPX4:glutathione peroxidase 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_002085.5(GPX4):c.438_441del (p.Lys145_Trp146insTer)

HGVS:

NC_000019.10:g.1105771_1105774del
NG_050621.1:g.6846_6849del
NM_001039847.3:c.438_441del
NM_001039848.4:c.549_552del
NM_001367832.1:c.357_360del
NM_002085.5:c.438_441delMANE SELECT
NP_001034936.1:p.Lys145_Trp146insTer
NP_001034937.1:p.Lys182_Trp183insTer
NP_001354761.1:p.Lys118_Trp119insTer
NP_002076.2:p.Lys145_Trp146insTer
NC_000019.9:g.1105768_1105771del
NC_000019.9:g.1105770_1105773del

Links:

dbSNP: rs772394824

NCBI 1000 Genomes Browser:

rs772394824

Molecular consequence:

NM_001039847.3:c.438_441del - nonsense - [Sequence Ontology: SO:0001587]
NM_001039848.4:c.549_552del - nonsense - [Sequence Ontology: SO:0001587]
NM_001367832.1:c.357_360del - nonsense - [Sequence Ontology: SO:0001587]
NM_002085.5:c.438_441del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002191589	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24706940, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002191589

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 13, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia.

Smith AC, Mears AJ, Bunker R, Ahmed A, MacKenzie M, Schwartzentruber JA, Beaulieu CL, Ferretti E; FORGE Canada Consortium., Majewski J, Bulman DE, Celik FC, Boycott KM, Graham GE.

J Med Genet. 2014 Jul;51(7):470-4. doi: 10.1136/jmedgenet-2013-102218. Epub 2014 Apr 4.

PubMed [citation]

PMID:: 24706940

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, SCV002191589.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with GPX4-related conditions. This variant is present in population databases (rs772394824, gnomAD 0.07%). This sequence change creates a premature translational stop signal (p.Trp183fs*1) in the GPX4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GPX4 are known to be pathogenic (PMID: 24706940). For these reasons, this variant has been 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: Feb 20, 2024

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