chr19-1226528-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000455.5(STK11):āc.1183A>Gā(p.Thr395Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,608,630 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. T395P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.1183A>G | p.Thr395Ala | missense_variant | 9/10 | ENST00000326873.12 | |
STK11 | NR_176325.1 | n.2450A>G | non_coding_transcript_exon_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.1183A>G | p.Thr395Ala | missense_variant | 9/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000846 AC: 2AN: 236316Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129820
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456404Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 724170
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The p.T395A variant (also known as c.1183A>G), located in coding exon 9 of the STK11 gene, results from an A to G substitution at nucleotide position 1183. The threonine at codon 395 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 04, 2023 | This missense variant replaces threonine with alanine at codon 395 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 2/236316 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. - |
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 | May 19, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 141954). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs587782138, gnomAD 0.001%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 395 of the STK11 protein (p.Thr395Ala). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 07, 2021 | - - |
Peutz-Jeghers syndrome;C0235974:Carcinoma of pancreas;C1336708:Germ cell tumor of testis;C1835047:Melanoma, cutaneous malignant, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 16, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at