rs587782287
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_000455.5(STK11):c.1120G>A(p.Glu374Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,610,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E374Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.1120G>A | p.Glu374Lys | missense_variant | 9/10 | ENST00000326873.12 | |
STK11 | NR_176325.1 | n.2387G>A | non_coding_transcript_exon_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.1120G>A | p.Glu374Lys | missense_variant | 9/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241280Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132334
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458732Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725546
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the STK11 protein (p.Glu374Lys). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 428789). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function with a negative predictive value of 95%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 15, 2023 | This missense variant replaces glutamic acid with lysine at codon 374 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders in the literature. This variant has been identified in 1/241280 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The p.E374K variant (also known as c.1120G>A), located in coding exon 9 of the STK11 gene, results from a G to A substitution at nucleotide position 1120. The glutamic acid at codon 374 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at