rs764449808
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_000455.5(STK11):āc.368A>Gā(p.Gln123Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q123E) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.368A>G | p.Gln123Arg | missense_variant | 2/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.368A>G | p.Gln123Arg | missense_variant | 2/9 | ||
STK11 | NR_176325.1 | n.1635A>G | non_coding_transcript_exon_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.368A>G | p.Gln123Arg | missense_variant | 2/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152270Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249032Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135202
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1461126Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726836
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74396
ClinVar
Submissions by phenotype
Squamous cell lung carcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | May 13, 2016 | - - |
Peutz-Jeghers syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2023 | 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. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 19892943). 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 expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 376709). This variant is also known as LKB1. This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs764449808, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 123 of the STK11 protein (p.Gln123Arg). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 04, 2020 | This missense variant replaces glutamine with arginine at codon 123 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/280426 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at