ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.1041G>A (p.Ala347=)
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(1); Benign(5); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000455.5(STK11):c.1041G>A (p.Ala347=)
Variation ID: 184691 Accession: VCV000184691.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19p13.3 19: 1223105 (GRCh38) [ NCBI UCSC ] 19: 1223104 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Mar 24, 2015 May 1, 2024 Jan 28, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000455.5:c.1041G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000446.1:p.Ala347= synonymous NC_000019.10:g.1223105G>A NC_000019.9:g.1223104G>A NG_007460.2:g.38699G>A LRG_319:g.38699G>A LRG_319t1:c.1041G>A LRG_319p1:p.Ala347= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000019.10:1223104:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00012
1000 Genomes Project 30x 0.00016
Exome Aggregation Consortium (ExAC) 0.00018
1000 Genomes Project 0.00020
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2390 | 2668 | |
LOC130062899 | - | - | - | GRCh38 | - | 216 |
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. |
---|---|---|---|---|
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 6, 2020 | RCV000163988.6 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 28, 2024 | RCV000233264.14 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 12, 2015 | RCV000220705.1 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 20, 2017 | RCV000587275.5 | |
Likely benign (1) |
no assertion criteria provided
|
- | RCV001358350.2 | |
STK11-related disorder
|
Likely benign (1) |
criteria provided, single submitter
|
Mar 17, 2020 | RCV003937503.1 |
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. |
|
---|---|---|---|---|---|
Likely benign
(Jun 06, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902985.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
Benign
(Sep 20, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888634.2
First in ClinVar: Mar 17, 2018 Last updated: Jan 01, 2022 |
|
|
Benign
(Apr 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004017919.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
|
|
Benign
(Jan 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000284840.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
|
|
Likely benign
(Dec 23, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000214588.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Uncertain significance
(Oct 12, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000279184.8
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
This variant is denoted STK11 c.1041G>A at the DNA level. Although the variant is silent at the coding level, preserving an Alanine at codon 347, … (more)
This variant is denoted STK11 c.1041G>A at the DNA level. Although the variant is silent at the coding level, preserving an Alanine at codon 347, this variant has been identified in at least one individual with hamartomatous polyps and was suggested to result in abnormal splicing (Wei 2003, Amos 2004); however, splicing models at our laboratory do not predict an effect on splicing. STK11 c.1041G>A was not observed at a significant allele frequency in 1000 Genomes. The nucleotide which is altered, a guanine (G) at base 1041, is not conserved across species. Based on currently available information, it is unclear whether STK11 c.1041G>A is pathogenic or benign. We consider this to be a variant of uncertain significance. (less)
|
|
Benign
(May 08, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696700.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The STK11 c.1041G>A (p.Ala347Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a … (more)
Variant summary: The STK11 c.1041G>A (p.Ala347Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts no significant changes in ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. Although the variant has been identified in at least one individual with hamartomatous polyps and was suggested to result in abnormal splicing (Wei 2003, Amos 2004), these studies provided no functional evidence to that effect and this report predated the development of large scale control population databases. The variant was found in the large control database ExAC in 17 of 95258 control chromosomes from all ethnicities, but was predominantly observed in the South Asian subpopulation at a frequency of 0.001139 (15/13164). This frequency is about 73 times the estimated maximal expected allele frequency of a pathogenic STK11 variant (0.0000156), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. Multiple clinical diagnostic laboratories have classified this variant with conflicting interpretations, including uncertain significance (1x in ClinVar), likely benign (1x in ClinVar), and benign (1x in ClinVar). Taken together, this variant is classified as benign. (less)
|
|
Likely benign
(Mar 21, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000785044.2
First in ClinVar: Jul 14, 2018 Last updated: Jul 14, 2018 |
|
|
Benign
(Oct 06, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531623.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
Likely benign
(Mar 17, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
STK11-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004765754.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Carcinoma of colon
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001554055.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The STK11 p.Ala347Ala variant was identified in 1 of 84 proband chromosomes (frequency: 0.01) from individuals or families with Peutz-Jaghers Syndrome (Amos 2004). The variant … (more)
The STK11 p.Ala347Ala variant was identified in 1 of 84 proband chromosomes (frequency: 0.01) from individuals or families with Peutz-Jaghers Syndrome (Amos 2004). The variant was identified in dbSNP (rs537906142) as “with likely benign, uncertain significance allele”, in ClinVar (interpreted as "benign" by Invitae and 2 others, "likely benign" by Ambry Genetics and "uncertain significance" by GeneDx). The variant was not identified in LOVD 3.0. The variant was identified in control databases in 27 of 241,514 chromosomes at a frequency of 0.0001 increasing the likelihood this could be a low frequency benign variant as this frequency is well above the known prevalence of Peutz-Jagher Syndrome (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 109,548 chromosomes (freq: 0.000009), Finnish in 1 of 21,340 chromosomes (freq: 0.00005), and South Asian in 25 of 30,278 chromosomes (freq: 0.0008). The variant was not observed in the African, Other, Latino, Ashkenazi Jewish, or East Asian populations. The p.Ala347= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicted the creation of a new splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
The genomic landscape of pediatric Ewing sarcoma. | Crompton BD | Cancer discovery | 2014 | PMID: 25186949 |
Genotype-phenotype correlations in Peutz-Jeghers syndrome. | Amos CI | Journal of medical genetics | 2004 | PMID: 15121768 |
Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome. | Wei C | The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society | 2003 | PMID: 14623934 |
Text-mined citations for rs537906142 ...
HelpRecord last updated Jun 23, 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.