rs587781966

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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81
Variant links:
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]

Genome browser will be placed here

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
STK11NM_000455.5 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 8/10 ENST00000326873.12 NP_000446.1
STK11NM_001407255.1 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 8/9 NP_001394184.1
STK11NR_176325.1 linkuse as main transcriptn.2219G>A non_coding_transcript_exon_variant 9/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 8/101 NM_000455.5 ENSP00000324856 P1Q15831-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152136
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1426812
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
706146
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74318
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 10, 2022This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
15
DANN
Benign
0.66
DEOGEN2
Benign
0.23
T;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.098
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.90
.;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.41
.;N
REVEL
Benign
0.15
Sift
Benign
0.54
.;T
Sift4G
Benign
0.53
T;T
Polyphen
0.0
.;B
Vest4
0.099
MutPred
0.20
Gain of glycosylation at A318 (P = 0.0058);Gain of glycosylation at A318 (P = 0.0058);
MVP
0.42
MPC
0.040
ClinPred
0.041
T
GERP RS
0.25
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.040
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587781966; hg19: chr19-1223015; API