NM_001395413.1(POR):c.1434C>A (p.Tyr478Ter) AND Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 18, 2023
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:: RCV003768629.2

Allele description [Variation Report for NM_001395413.1(POR):c.1434C>A (p.Tyr478Ter)]

NM_001395413.1(POR):c.1434C>A (p.Tyr478Ter)

Gene:

POR:cytochrome p450 oxidoreductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.23

Genomic location:

Preferred name:

NM_001395413.1(POR):c.1434C>A (p.Tyr478Ter)

HGVS:

NC_000007.14:g.75985623C>A
NG_008930.1:g.75522C>A
NM_001367562.3:c.1434C>A
NM_001382655.3:c.1488C>A
NM_001382657.2:c.1434C>A
NM_001382658.3:c.1434C>A
NM_001382659.3:c.1434C>A
NM_001382662.3:c.1284C>A
NM_001395413.1:c.1434C>AMANE SELECT
NP_001354491.2:p.Tyr478Ter
NP_001369584.2:p.Tyr496Ter
NP_001369586.2:p.Tyr478Ter
NP_001369587.2:p.Tyr478Ter
NP_001369588.2:p.Tyr478Ter
NP_001369591.2:p.Tyr428Ter
NP_001382342.1:p.Tyr478Ter
NC_000007.13:g.75614941C>A
NC_000007.13:g.75614941C>A
NM_000941.2:c.1443C>A

Protein change:

Y428*

Links:

dbSNP: rs373613946

NCBI 1000 Genomes Browser:

rs373613946

Molecular consequence:

NM_001367562.3:c.1434C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001382655.3:c.1488C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001382657.2:c.1434C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001382658.3:c.1434C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001382659.3:c.1434C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001382662.3:c.1284C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001395413.1:c.1434C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
Synonyms:: DISORDERED STEROIDOGENESIS DUE TO POR DEFICIENCY; Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency
Identifiers:: MONDO: MONDO:0013310; MedGen: C1860042; OMIM: 613571

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004680487	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 14758361, 20732302, 21741353, 31837199, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004680487

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2023)

germline

clinical testing

PubMed (5)
[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

Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome.

Flück CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonça BB, Fujieda K, Miller WL.

Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1.

PubMed [citation]

PMID:: 14758361

Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase.

Pandey AV, Flück CE, Mullis PE.

Biochem Biophys Res Commun. 2010 Sep 24;400(3):374-8. doi: 10.1016/j.bbrc.2010.08.072. Epub 2010 Aug 21.

PubMed [citation]

PMID:: 20732302

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004680487.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Tyr481*) in the POR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POR are known to be pathogenic (PMID: 14758361, 20732302, 21741353). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of Antley-Bixler syndrome (PMID: 31837199). ClinVar contains an entry for this variant (Variation ID: 691923). 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: Sep 29, 2024

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