NM_001395413.1(POR):c.850G>C (p.Ala284Pro) AND Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 12, 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:: RCV000018401.32

Allele description [Variation Report for NM_001395413.1(POR):c.850G>C (p.Ala284Pro)]

NM_001395413.1(POR):c.850G>C (p.Ala284Pro)

Genes:

LOC126860075:CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:75612087-75613286 [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.850G>C (p.Ala284Pro)

Other names:

A287P; A284P

HGVS:

NC_000007.14:g.75983548G>C
NG_008930.1:g.73447G>C
NM_000941.3:c.859G>C
NM_001367562.3:c.850G>C
NM_001382655.3:c.904G>C
NM_001382657.2:c.850G>C
NM_001382658.3:c.850G>C
NM_001382659.3:c.850G>C
NM_001382662.3:c.850G>C
NM_001395413.1:c.850G>CMANE SELECT
NP_001354491.2:p.Ala284Pro
NP_001369584.2:p.Ala302Pro
NP_001369586.2:p.Ala284Pro
NP_001369587.2:p.Ala284Pro
NP_001369588.2:p.Ala284Pro
NP_001369591.2:p.Ala284Pro
NP_001382342.1:p.Ala284Pro
NC_000007.13:g.75612866G>C
NM_000941.2:c.859G>C

Protein change:

A302P; ALA287PRO

Links:

OMIM: 124015.0002; dbSNP: rs121912974

NCBI 1000 Genomes Browser:

rs121912974

Molecular consequence:

NM_001367562.3:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382655.3:c.904G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382657.2:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382658.3:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382659.3:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382662.3:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001395413.1:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1)
Synonyms:: POR Deficiency
Identifiers:: MONDO: MONDO:0008726; MedGen: C3150099; OMIM: 201750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038683	OMIM	no assertion criteria provided	Pathogenic (May 1, 2005)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 14758361, 12116245, 15793702, 15220035
SCV001167495	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	no assertion criteria provided	Uncertain significance	inherited	research
SCV003807528	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038683

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2005)

germline

literature only

PubMed (4)
[See all records that cite these PMIDs]

SCV001167495

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

no assertion criteria provided

Uncertain significance

inherited

research

SCV003807528

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 12, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	3	1	not provided	not provided	yes	research
not provided	germline	yes	1	not provided	not provided	1	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

Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia.

Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW.

Am J Med Genet. 2002 Jun 15;110(2):95-102.

PubMed [citation]

PMID:: 12116245

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000038683.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

In a child with bony features of Antley-Bixler syndrome with genital ambiguity and abnormal steroidogenesis (ABS1; 201750), Fluck et al. (2004) found apparent homozygosity for a nucleotide substitution 859G-C in the POR gene leading to an ala287-to-pro (A287P) substitution. This child had been described by Kelley et al. (2002). The mother was heterozygous for the mutation; paternal DNA was not available.

Huang et al. (2005) sequenced the POR gene in 29 individuals with Antley-Bixler syndrome and/or hormonal findings that suggested POR deficiency. Fifteen patients carried POR mutations on both alleles; 4 carried mutations on only 1 allele. The 34 affected POR alleles included 10 with A287P, all in Caucasians.

For discussion of the A287P mutation in the POR gene that was found in compound heterozygous state in a patient with congenital adrenal hyperplasia due to apparent combined deficiency of P450C17 and P450C21 (613571) by Arlt et al. (2004), see 124015.0005.

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

From Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV001167495.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	yes	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		3	not provided	1	not provided

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV003807528.1

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

Description

ACMG classification criteria: PS3 supporting, PM3 very strong, PP3 supporting

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

Last Updated: May 12, 2024

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