ClinVar Genomic variation as it relates to human health
NM_003764.4(STX11):c.616G>A (p.Glu206Lys)
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_003764.4(STX11):c.616G>A (p.Glu206Lys)
Variation ID: 403500 Accession: VCV000403500.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q24.2 6: 144187243 (GRCh38) [ NCBI UCSC ] 6: 144508380 (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 Apr 9, 2017 Feb 7, 2023 Oct 17, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003764.4:c.616G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003755.2:p.Glu206Lys missense NC_000006.12:g.144187243G>A NC_000006.11:g.144508380G>A NG_007613.1:g.41727G>A LRG_113:g.41727G>A LRG_113t1:c.616G>A - Protein change
- E206K
- Other names
- -
- Canonical SPDI
- NC_000006.12:144187242:G:A
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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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0.00080 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00080
The Genome Aggregation Database (gnomAD) 0.00086
Trans-Omics for Precision Medicine (TOPMed) 0.00103
The Genome Aggregation Database (gnomAD), exomes 0.00107
1000 Genomes Project 30x 0.00109
Exome Aggregation Consortium (ExAC) 0.00110
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00161
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
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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STX11 | - | - |
GRCh38 GRCh37 |
387 | 408 |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Uncertain significance (1) |
criteria provided, single submitter
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Apr 25, 2016 | RCV000454862.4 | |
not provided (2) |
no classification provided
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- | RCV000509480.2 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Oct 17, 2022 | RCV000779494.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 3, 2019 | RCV001584124.3 |
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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Uncertain significance
(Apr 25, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540472.1
First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: seen in MedSeq case (less)
Method: Genome/Exome Filtration
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Uncertain significance
(Aug 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000916127.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The STX11 c.616G>A (p.Glu206Lys) missense variant has been reported in one study in a compound heterozygous state in one individual who presented with familial hemophagocytic … (more)
The STX11 c.616G>A (p.Glu206Lys) missense variant has been reported in one study in a compound heterozygous state in one individual who presented with familial hemophagocytic lymphohistiocytosis at age five years (Marsh et al. 2010). The p.Glu206Lys variant was absent from 50 controls but is reported at a frequency of 0.00336 in the Other population of the Exome Aggregation Consortium. In vitro experiments using peripheral blood mononuclear cells from the compound heterozygous patient demonstrated a detectable mutated syntaxin 11 protein, but the NK cell degranulation and cytotoxicity activity was preserved (Marsh et al. 2010). Based on the limited evidence, the Glu206Lys variant is classified as a variant of unknown significance but suspicious for pathogenicity for familial hemophagocytic lymphohistiocytosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Uncertain significance
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 4
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137251.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Sep 03, 2019)
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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: SCV001811668.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Identified in trans with another missense variant in an individual with clinical features of familial hemophagocytic lymphohistiocytosis in the published literature (Marsh et al., 2010); … (more)
Identified in trans with another missense variant in an individual with clinical features of familial hemophagocytic lymphohistiocytosis in the published literature (Marsh et al., 2010); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20486178) (less)
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Uncertain significance
(May 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 4
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768547.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
A heterozygous missense variant was identified, NM_003764.3(STX11):c.616G>A in exon 2 of 2 of the STX11 gene. This substitution is predicted to create a minor amino … (more)
A heterozygous missense variant was identified, NM_003764.3(STX11):c.616G>A in exon 2 of 2 of the STX11 gene. This substitution is predicted to create a minor amino acid change from a glutamic acid to a lysine at position 206 of the protein; NP_003755.2(STX11):p.(Glu206Lys). The glutamic acid at this position has moderate conservation (100 vertebrates, UCSC), and is located within the t-SNARE coiled-coil region of the protein (PDB, UniProt). In silico software predicts this variant to be damaging (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a global population frequency of of 0.1% (289 heterozygotes, 0 homozygotes) with a European sub-population frequency of 0.17%. This variant has previously been reported as a VUS in patients with haemophagocytic lymphohistiocytosis and was shown to be a compound heterozygote in a patient (ClinVar, Marsh, R. et al. (2010)). Based on information available at the time of curation, this variant has been classified as a VUS with POTENTIAL CLINICAL RELEVANCE. (less)
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Uncertain significance
(Oct 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 4
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000949820.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 206 of the STX11 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 206 of the STX11 protein (p.Glu206Lys). This variant is present in population databases (rs145347140, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 20486178). ClinVar contains an entry for this variant (Variation ID: 403500). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on STX11 function (PMID: 20486178). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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not provided
(-)
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no classification provided
Method: phenotyping only
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Familial hemophagocytic lymphohistiocytosis
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV000607347.1
First in ClinVar: Oct 16, 2017 Last updated: Oct 16, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Myopia (present)
Age: 30-39 years
Sex: female
Testing laboratory: Illumina Clinical Services Laboratory,Illumina
Date variant was reported to submitter: 2014-10-24
Testing laboratory interpretation: Uncertain significance
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not provided
(-)
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no classification provided
Method: phenotyping only
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Familial hemophagocytic lymphohistiocytosis
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749507.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Uncertain significance and reported on 04-01-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Uncertain significance and reported on 04-01-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal oral cavity morphology (present) , Abnormality of the mouth (present) , Asthma (present) , Abnormal inflammatory response (present) , Recurrent infections (present) , Abnormality … (more)
Abnormal oral cavity morphology (present) , Abnormality of the mouth (present) , Asthma (present) , Abnormal inflammatory response (present) , Recurrent infections (present) , Abnormality of the amniotic fluid (present) , Pregnancy history (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-04-01
Testing laboratory interpretation: Uncertain significance
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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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STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. | Marsh RA | Pediatric blood & cancer | 2010 | PMID: 20486178 |
Text-mined citations for rs145347140 ...
HelpRecord last updated Dec 30, 2023
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.