ClinVar Genomic variation as it relates to human health
NM_000198.4(HSD3B2):c.1003C>T (p.Arg335Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000198.4(HSD3B2):c.1003C>T (p.Arg335Ter)
Variation ID: 597649 Accession: VCV000597649.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p12 1: 119422504 (GRCh38) [ NCBI UCSC ] 1: 119965127 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 17, 2018 Apr 6, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000198.4:c.1003C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000189.1:p.Arg335Ter nonsense NM_001166120.2:c.1003C>T NP_001159592.1:p.Arg335Ter nonsense NC_000001.11:g.119422504C>T NC_000001.10:g.119965127C>T NG_013349.1:g.12574C>T - Protein change
- R335*
- Other names
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- Canonical SPDI
- NC_000001.11:119422503:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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HSD3B2 | - | - |
GRCh38 GRCh37 |
308 | 372 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2023 | RCV000733829.11 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 26, 2024 | RCV001830636.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000861929.1
First in ClinVar: Dec 17, 2018 Last updated: Dec 17, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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3 beta-Hydroxysteroid dehydrogenase deficiency
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521674.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Stop-gained (nonsense): predicted to result in a … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000597649). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Episodic vomiting (present) , Dehydration (present) , Ambiguous genitalia (present) , Elevated circulating 17-hydroxyprogesterone concentration (present) , Hyponatremia (present) , Hyperkalemia (present)
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Pathogenic
(Feb 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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3 beta-Hydroxysteroid dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002782892.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001411152.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg335*) in the HSD3B2 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg335*) in the HSD3B2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the HSD3B2 protein. This variant is present in population databases (rs148200568, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital adrenal hyperplasia and clinical features of congenital adrenal hyperplasia (PMID: 18252794, 31006099). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 597649). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects HSD3B2 function (PMID: 18252794). This variant disrupts the C-terminus of the HSD3B2 protein, which has been demonstrated to be critical for enzymatic activity (PMID: 1825279). While functional studies have not been performed to directly test the effect of this variant on HSD3B2 protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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3 beta-Hydroxysteroid dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806968.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Apr 23, 2021)
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no assertion criteria provided
Method: clinical testing
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3 beta hydroxysteroid dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002094678.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The molecular basis and genotype-phenotype correlations of congenital adrenal hyperplasia (CAH) in Anatolian population. | Dundar A | Molecular biology reports | 2019 | PMID: 31006099 |
Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. | Welzel M | The Journal of clinical endocrinology and metabolism | 2008 | PMID: 18252794 |
Radiation therapy in the management of skin cancers. | Toce J | Dermatology nursing | 1991 | PMID: 1825279 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HSD3B2 | - | - | - | - |
Text-mined citations for rs148200568 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.