NM_000781.3(CYP11A1):c.391C>T (p.Gln131Ter) AND Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 25, 2019
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:: RCV001195422.4

Allele description [Variation Report for NM_000781.3(CYP11A1):c.391C>T (p.Gln131Ter)]

NM_000781.3(CYP11A1):c.391C>T (p.Gln131Ter)

Gene:

CYP11A1:cytochrome P450 family 11 subfamily A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_000781.3(CYP11A1):c.391C>T (p.Gln131Ter)

HGVS:

NC_000015.10:g.74347934G>A
NG_007973.1:g.24808C>T
NM_000781.3:c.391C>TMANE SELECT
NM_001099773.2:c.-84C>T
NP_000772.2:p.Gln131Ter
NC_000015.9:g.74640275G>A

Protein change:

Q131*

Links:

dbSNP: rs2060639501

NCBI 1000 Genomes Browser:

rs2060639501

Molecular consequence:

NM_001099773.2:c.-84C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000781.3:c.391C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency
Synonyms:: P450scc DEFICIENCY; Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
Identifiers:: MONDO: MONDO:0013400; MedGen: C3151055; Orphanet: 168558; OMIM: 613743

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001365773	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Jul 25, 2019)	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

SCV001365773

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Jul 25, 2019)

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	unknown	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001365773.1

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

Description

The p.Gln131X variant in CYP11A1 has not been previously reported in individuals with adrenal insufficiency and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 131, which is predicted to lead to a truncated or absent protein. Loss of function of the CYP11A1 gene is an established disease mechanism in autosomal recessive congenital adrenal insufficiency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive congenital adrenal insufficiency. ACMG/AMP Criteria applied: PVS1, PM2.

#	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		1	not provided	1	not provided

Last Updated: Dec 24, 2022

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