rs1060499969
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000455.5(STK11):c.1037_1042del(p.Gly346_Ala347del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000186 in 1,610,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G346G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
STK11
NM_000455.5 inframe_deletion
NM_000455.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.51
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
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Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_000455.5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.1037_1042del | p.Gly346_Ala347del | inframe_deletion | 8/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.1037_1042del | p.Gly346_Ala347del | inframe_deletion | 8/9 | ||
STK11 | NR_176325.1 | n.2304_2309del | non_coding_transcript_exon_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.1037_1042del | p.Gly346_Ala347del | inframe_deletion | 8/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243400Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132654
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458686Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725416
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | This variant, c.1037_1042del, results in the deletion of 2 amino acid(s) of the STK11 protein (p.Gly346_Ala347del), but otherwise preserves the integrity of the reading frame. 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: 403793). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2023 | The c.1037_1042delGCGCGG variant (also known as p.G346_A347del) is located in coding exon 8 of the STK11 gene. This variant results from an in-frame GCGCGG deletion at nucleotide positions 1037 to 1042. This results in the in-frame deletion of a glycine and an alanine residue at codons 346 to 347. This variant was identified in a cohort of 882 Chinese individuals with a personal and/or family history of breast or ovarian cancers who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This amino acid region is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 11, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 06, 2020 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at