19-1226598-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000455.5(STK11):c.1253G>A(p.Cys418Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C418S) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 missense
Scores
Clinical Significance
Conservation
Publications
- familial pancreatic carcinomaInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Peutz-Jeghers syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.1253G>A | p.Cys418Tyr | missense_variant | Exon 9 of 10 | ENST00000326873.12 | NP_000446.1 | |
STK11 | NR_176325.1 | n.2520G>A | non_coding_transcript_exon_variant | Exon 10 of 11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.1253G>A | p.Cys418Tyr | missense_variant | Exon 9 of 10 | 1 | NM_000455.5 | ENSP00000324856.6 | ||
STK11 | ENST00000585748.3 | c.881G>A | p.Cys294Tyr | missense_variant | Exon 11 of 12 | 3 | ENSP00000477641.2 | |||
STK11 | ENST00000593219.6 | n.*1078G>A | non_coding_transcript_exon_variant | Exon 10 of 11 | 3 | ENSP00000466610.1 | ||||
STK11 | ENST00000593219.6 | n.*1078G>A | 3_prime_UTR_variant | Exon 10 of 11 | 3 | ENSP00000466610.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.08e-7 AC: 1AN: 1412108Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1AN XY: 698300 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:1
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 418 of the STK11 protein (p.Cys418Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 657657). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at