ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.464+3G>A
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.
Uncertain significance(4); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000455.5(STK11):c.464+3G>A
Variation ID: 403768 Accession: VCV000403768.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.3 19: 1219416 (GRCh38) [ NCBI UCSC ] 19: 1219415 (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 17, 2017 May 1, 2024 Oct 6, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000455.5:c.464+3G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000019.10:g.1219416G>A NC_000019.9:g.1219415G>A NG_007460.2:g.35010G>A LRG_319:g.35010G>A LRG_319t1:c.464+3G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000019.10:1219415: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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
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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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STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2350 | 2623 |
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
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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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Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Oct 6, 2023 | RCV000474445.11 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Mar 1, 2023 | RCV000581483.9 |
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
(Oct 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000541125.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change falls in intron 3 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein. … (more)
This sequence change falls in intron 3 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 403768). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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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Likely benign
(Apr 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004017950.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
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Likely Benign
(Sep 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004828575.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 1
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Uncertain significance
(Mar 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000786207.2
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
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Likely benign
(Jun 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000691506.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Uncertain significance
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001184611.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The c.464+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 3 in the STK11 gene. This nucleotide position is … (more)
The c.464+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 3 in the STK11 gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002057243.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 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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Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs1060499956 ...
HelpRecord last updated May 08, 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.