NM_000349.3(STAR):c.574C>T (p.Arg192Cys) AND Congenital lipoid adrenal hyperplasia due to STAR deficency

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 7, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000666231.3

Allele description [Variation Report for NM_000349.3(STAR):c.574C>T (p.Arg192Cys)]

NM_000349.3(STAR):c.574C>T (p.Arg192Cys)

Gene:

STAR:steroidogenic acute regulatory protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.23

Genomic location:

Preferred name:

NM_000349.3(STAR):c.574C>T (p.Arg192Cys)

HGVS:

NC_000008.11:g.38146039G>A
NG_011827.1:g.10044C>T
NM_000349.3:c.574C>TMANE SELECT
NP_000340.2:p.Arg192Cys
NC_000008.10:g.38003557G>A
NM_000349.2:c.574C>T

Protein change:

R192C

Links:

dbSNP: rs752311616

NCBI 1000 Genomes Browser:

rs752311616

Molecular consequence:

NM_000349.3:c.574C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital lipoid adrenal hyperplasia due to STAR deficency
Synonyms:: ADRENAL HYPERPLASIA I; Congenital lipoid adrenal hyperplasia; Lipoid CAH; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008725; MedGen: C0342474; Orphanet: 418; OMIM: 201710

Recent activity

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pleckstrin homology-like domain family A member 2 [Mus musculus]
pleckstrin homology-like domain family A member 2 [Mus musculus]
gi|6678447|ref|NP_033460.1|

Protein
dab21h04.x1 NICHD_XGC_Sp1 Xenopus laevis cDNA clone IMAGE:4175095 3' similar to ...
dab21h04.x1 NICHD_XGC_Sp1 Xenopus laevis cDNA clone IMAGE:4175095 3' similar to SW:AN12_COLLI Q92040 ANNEXIN I, ISOFORM P37, mRNA sequence
gi|13348673|gnl|dbEST|8141196|gb|BG 3.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000790489	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Apr 4, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20444910, 19773404, 21647419 Citation Link,
SCV004038287	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 7, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20444910, 19773404 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000790489

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Apr 4, 2017)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV004038287

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 7, 2023)

germline

clinical testing

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

Citation Link

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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

Characterization of novel StAR (steroidogenic acute regulatory protein) mutations causing non-classic lipoid adrenal hyperplasia.

Flück CE, Pandey AV, Dick B, Camats N, Fernández-Cancio M, Clemente M, Gussinyé M, Carrascosa A, Mullis PE, Audi L.

PLoS One. 2011;6(5):e20178. doi: 10.1371/journal.pone.0020178. Epub 2011 May 27.

PubMed [citation]

PMID:: 21647419
PMCID:: PMC3103540

Clinical, genetic, and functional characterization of four patients carrying partial loss-of-function mutations in the steroidogenic acute regulatory protein (StAR).

Sahakitrungruang T, Soccio RE, Lang-Muritano M, Walker JM, Achermann JC, Miller WL.

J Clin Endocrinol Metab. 2010 Jul;95(7):3352-9. doi: 10.1210/jc.2010-0437. Epub 2010 May 5. Erratum in: J Clin Endocrinol Metab. 2011 Dec;96(12):3908.

PubMed [citation]

PMID:: 20444910
PMCID:: PMC2928910

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000790489.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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, SCV004038287.1

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

Description

Variant summary: STAR c.574C>T (p.Arg192Cys) results in a non-conservative amino acid change located in the START domain (IPR002913) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251364 control chromosomes. c.574C>T has been reported in the literature in multiple individuals affected with Congenital Lipoid Adrenal Hyperplasia (Metherell_2009). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence demonstrating a decrease in activity and Cholesterol binding (Sahakitrungruang_2010). The following publications have been ascertained in the context of this evaluation (PMID: 19773404, 20444910). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. 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: Feb 20, 2024

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