19-1221273-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000455.5(STK11):c.795G>C(p.Glu265Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E265E) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.795G>C | p.Glu265Asp | missense_variant | Exon 6 of 10 | ENST00000326873.12 | NP_000446.1 | |
STK11 | NM_001407255.1 | c.795G>C | p.Glu265Asp | missense_variant | Exon 6 of 9 | NP_001394184.1 | ||
STK11 | NR_176325.1 | n.2062G>C | non_coding_transcript_exon_variant | Exon 7 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.795G>C | p.Glu265Asp | missense_variant | Exon 6 of 10 | 1 | NM_000455.5 | ENSP00000324856.6 | ||
STK11 | ENST00000652231.1 | c.795G>C | p.Glu265Asp | missense_variant | Exon 6 of 9 | ENSP00000498804.1 | ||||
STK11 | ENST00000585748.3 | c.423G>C | p.Glu141Asp | missense_variant | Exon 8 of 12 | 3 | ENSP00000477641.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246466Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134254
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459716Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726052
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:1
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. This variant has not been reported in the literature in individuals with STK11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 265 of the STK11 protein (p.Glu265Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at