rs376329042
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000455.5(STK11):c.945G>A(p.Pro315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,571,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P315P) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.945G>A | p.Pro315= | synonymous_variant | 8/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.945G>A | p.Pro315= | synonymous_variant | 8/9 | ||
STK11 | NR_176325.1 | n.2212G>A | non_coding_transcript_exon_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.945G>A | p.Pro315= | synonymous_variant | 8/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000624 AC: 95AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000789 AC: 151AN: 191344Hom.: 0 AF XY: 0.000725 AC XY: 75AN XY: 103392
GnomAD4 exome AF: 0.000951 AC: 1350AN: 1419262Hom.: 1 Cov.: 31 AF XY: 0.000922 AC XY: 647AN XY: 701450
GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000618 AC XY: 46AN XY: 74468
ClinVar
Submissions by phenotype
not provided Benign:6
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 06, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | STK11: BP4, BP7 - |
Peutz-Jeghers syndrome Benign:6
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not specified Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 19, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 21, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 01, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 09, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. | Oct 04, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Dec 01, 2017 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 20, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2014 | 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. - |
Breast and/or ovarian cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 05, 2023 | - - |
STK11-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 14, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Malignant tumor of breast Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The STK11 p.Pro315= variant was identified in 2 of 144 proband chromosomes (frequency: 0.01) from Spanish and Australian individuals or families with Lynch syndrome or PJS (Peutz–Jeghers syndrome (Vargas-Parra_2017_28577310, Scott_2002_12372054 ). The variant was also identified in dbSNP (ID: rs376329042) “With Likely benign allele”, ClinVar (classified benign by Invitae, GeneDx, and Quest Diagnostics Nichols Institute San Juan Capistrano, and likely benign by Ambry Genetics), Clinvitae (3x), Cosmic (1x in a carcinoma of the large intestine), Zhejiang Colon Cancer Database (8x), and in control databases in 150 of 218304 chromosomes at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3 of 19118 chromosomes (freq: 0.0002), Other in 3 of 5448 chromosomes (freq: 0.0006), Latino in 10 of 28572 chromosomes (freq: 0.0004), European Non-Finnish in 66 of 95490 chromosomes (freq: 0.0007), Ashkenazi Jewish in 48 of 8990 chromosomes (freq: 0.005), European Finnish in 2 of 20554 chromosomes (freq: 0.0001), and South Asian in 18 of 25328 chromosomes (freq: 0.0007) while not observed in the East Asian population. The variant was not identified in MutDB, LOVD 3.0, and Insight Hereditary Tumors Database The p.Pro315= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at