ClinVar Genomic variation as it relates to human health
NM_213622.4(STAMBP):c.112C>T (p.Arg38Cys)
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_213622.4(STAMBP):c.112C>T (p.Arg38Cys)
Variation ID: 50793 Accession: VCV000050793.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.1 2: 73830968 (GRCh38) [ NCBI UCSC ] 2: 74058095 (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 Nov 23, 2014 Apr 15, 2024 Jun 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_213622.4:c.112C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_998787.1:p.Arg38Cys missense NM_001353967.2:c.112C>T NP_001340896.1:p.Arg38Cys missense NM_001353968.2:c.112C>T NP_001340897.1:p.Arg38Cys missense NM_001353969.2:c.112C>T NP_001340898.1:p.Arg38Cys missense NM_001353970.2:c.112C>T NP_001340899.1:p.Arg38Cys missense NM_001353971.2:c.-442C>T 5 prime UTR NM_001353972.2:c.-203+1972C>T intron variant NM_001353973.2:c.-442C>T 5 prime UTR NM_001353974.2:c.-442C>T 5 prime UTR NM_001353975.2:c.-442C>T 5 prime UTR NM_001353976.2:c.-442C>T 5 prime UTR NM_006463.6:c.112C>T NP_006454.1:p.Arg38Cys missense NM_201647.4:c.112C>T NP_964010.1:p.Arg38Cys missense NR_148668.2:n.160C>T non-coding transcript variant NR_148669.2:n.160C>T non-coding transcript variant NR_148670.2:n.340C>T non-coding transcript variant NR_148671.2:n.674C>T non-coding transcript variant NC_000002.12:g.73830968C>T NC_000002.11:g.74058095C>T NG_033223.2:g.7058C>T O95630:p.Arg38Cys - Protein change
- R38C
- Other names
- NM_006463.4(STAMBP):c.112C>T(p.Arg38Cys)
- NM_201647.2(STAMBP):c.112C>T(p.Arg38Cys)
- NM_213622.2(STAMBP):c.112C>T(p.Arg38Cys)
- Canonical SPDI
- NC_000002.12:73830967: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00009
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
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
Help
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
Help
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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LOC126806253 | - | - | - | GRCh38 | - | 34 |
STAMBP | - | - |
GRCh38 GRCh37 |
157 | 203 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
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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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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May 31, 2018 | RCV000043574.14 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 26, 2023 | RCV000426675.23 |
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
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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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Likely pathogenic
(May 31, 2018)
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criteria provided, single submitter
Method: curation
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Microcephaly-capillary malformation syndrome
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV000803509.1
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
This variant is interpreted as a Likely Pathogenic, for Microcephaly-capillary malformation syndrome, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM3 => For … (more)
This variant is interpreted as a Likely Pathogenic, for Microcephaly-capillary malformation syndrome, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:23542699). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:23542699). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Supporting => PS4 downgraded in strength to Supporting (PMID:23542699). (less)
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Likely pathogenic
(Jun 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000517314.7
First in ClinVar: Mar 08, 2017 Last updated: Jul 01, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23542699, 32929933, 35723786, 35962715, 33149276) (less)
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Pathogenic
(Aug 07, 2022)
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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: SCV003271218.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 50793). This missense change has been observed in individual(s) with microcephaly-capillary malformation syndrome (PMID: 23542699). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs143739249, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 38 of the STAMBP protein (p.Arg38Cys). (less)
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Pathogenic
(Jul 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248156.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Dec 30, 2013)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly-capillary malformation syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000195120.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Likely pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447691.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Hypotonia (present) , Global developmental delay (present) , Plagiocephaly (present) , Developmental regression (present) , Seizure (present)
Sex: male
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Pathogenic
(May 01, 2013)
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no assertion criteria provided
Method: literature only
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MICROCEPHALY-CAPILLARY MALFORMATION SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000071444.5
First in ClinVar: Jun 05, 2013 Last updated: Oct 09, 2016 |
Comment on evidence:
In a boy of European descent with microcephaly-capillary malformation syndrome (MICCAP; 614261) reported by Mirzaa et al. (2011), McDonell et al. (2013) identified compound heterozygous … (more)
In a boy of European descent with microcephaly-capillary malformation syndrome (MICCAP; 614261) reported by Mirzaa et al. (2011), McDonell et al. (2013) identified compound heterozygous mutations in the STAMBP gene: a c.112C-T transition, resulting in an arg38-to-cys (R38C) substitution, and a c.279+5G-T splice site mutation (606247.0004), predicted to include an extra codon in exon 4, supporting a pathogenic effect. The mutations, which were identified by exome sequencing and were not found in several large control exome databases, segregated with the disorder. Another patient of Polynesian descent was compound heterozygous for R38C and a 1-bp deletion (c.411delC; 606247.0007), predicted to result in a frameshift and premature termination (Ile138SerfsTer12). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Microcephaly-capillary malformation syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
inherited
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001739508.1
First in ClinVar: Jul 07, 2021 Last updated: Jul 07, 2021 |
Sex: female
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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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Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. | McDonell LM | Nature genetics | 2013 | PMID: 23542699 |
The microcephaly-capillary malformation syndrome. | Mirzaa GM | American journal of medical genetics. Part A | 2011 | PMID: 21815250 |
Text-mined citations for rs143739249 ...
HelpRecord last updated Apr 15, 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.