rs587781966
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000455.5(STK11):c.952G>A(p.Ala318Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
STK11
NM_000455.5 missense
NM_000455.5 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: 1.81
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.097884536).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.952G>A | p.Ala318Thr | missense_variant | 8/10 | ENST00000326873.12 | NP_000446.1 | |
STK11 | NM_001407255.1 | c.952G>A | p.Ala318Thr | missense_variant | 8/9 | NP_001394184.1 | ||
STK11 | NR_176325.1 | n.2219G>A | non_coding_transcript_exon_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.952G>A | p.Ala318Thr | missense_variant | 8/10 | 1 | NM_000455.5 | ENSP00000324856 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152136Hom.: 0 Cov.: 33 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1426812Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 706146
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peutz-Jeghers syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 10, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 318 of the STK11 protein (p.Ala318Thr). 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. ClinVar contains an entry for this variant (Variation ID: 403773). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
MutPred
Gain of glycosylation at A318 (P = 0.0058);Gain of glycosylation at A318 (P = 0.0058);
MVP
MPC
0.040
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at