chr19-1206935-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000455.5(STK11):āc.22C>Gā(p.Gln8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,442,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q8H) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.22C>G | p.Gln8Glu | missense_variant | 1/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.22C>G | p.Gln8Glu | missense_variant | 1/9 | ||
STK11 | NR_176325.1 | n.1158C>G | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.22C>G | p.Gln8Glu | missense_variant | 1/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000463 AC: 1AN: 215880Hom.: 0 AF XY: 0.00000850 AC XY: 1AN XY: 117652
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1442788Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2AN XY: 716082
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 527816). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs760588289, gnomAD 0.001%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 8 of the STK11 protein (p.Gln8Glu). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | This missense variant replaces glutamine with glutamic acid at codon 8 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 1/215880 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:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 24, 2023 | This missense variant replaces glutamine with glutamic acid at codon 8 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 1/215880 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2018 | The p.Q8E variant (also known as c.22C>G), located in coding exon 1 of the STK11 gene, results from a C to G substitution at nucleotide position 22. The glutamine at codon 8 is replaced by glutamic acid, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at