19-1206998-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000455.5(STK11):c.85A>T(p.Ile29Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.85A>T | p.Ile29Phe | missense_variant | Exon 1 of 10 | ENST00000326873.12 | NP_000446.1 | |
STK11 | NM_001407255.1 | c.85A>T | p.Ile29Phe | missense_variant | Exon 1 of 9 | NP_001394184.1 | ||
STK11 | NR_176325.1 | n.1221A>T | non_coding_transcript_exon_variant | Exon 1 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.85A>T | p.Ile29Phe | missense_variant | Exon 1 of 10 | 1 | NM_000455.5 | ENSP00000324856.6 | ||
STK11 | ENST00000652231.1 | c.85A>T | p.Ile29Phe | missense_variant | Exon 1 of 9 | ENSP00000498804.1 | ||||
STK11 | ENST00000585748.3 | c.-82-11419A>T | intron_variant | Intron 3 of 11 | 3 | ENSP00000477641.2 | ||||
STK11 | ENST00000593219.5 | n.85A>T | non_coding_transcript_exon_variant | Exon 1 of 4 | 3 | ENSP00000466610.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726956
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Peutz-Jeghers syndrome Uncertain:1
This sequence change replaces isoleucine with phenylalanine at codon 29 of the STK11 protein (p.Ile29Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 221001). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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:1
The p.I29F variant (also known as c.85A>T), located in coding exon 1 of the STK11 gene, results from an A to T substitution at nucleotide position 85. The isoleucine at codon 29 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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