GeneBe

rs878853988

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_000455.5(STK11):​c.460C>A​(p.His154Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

STK11
NM_000455.5 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a domain Protein kinase (size 260) in uniprot entity STK11_HUMAN there are 19 pathogenic changes around while only 5 benign (79%) in NM_000455.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.460C>A p.His154Asn missense_variant Exon 3 of 10 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkc.460C>A p.His154Asn missense_variant Exon 3 of 9 NP_001394184.1
STK11NR_176325.1 linkn.1727C>A non_coding_transcript_exon_variant Exon 4 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.460C>A p.His154Asn missense_variant Exon 3 of 10 1 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkc.460C>A p.His154Asn missense_variant Exon 3 of 9 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkc.88C>A p.His30Asn missense_variant Exon 5 of 12 3 ENSP00000477641.2 A0A087WT72
STK11ENST00000593219.5 linkn.*285C>A downstream_gene_variant 3 ENSP00000466610.1 K7EMR0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1277730
Hom.:
0
Cov.:
39
AF XY:
0.00
AC XY:
0
AN XY:
634676
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T;D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.80
T;T
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Uncertain
0.041
D
MutationAssessor
Benign
0.80
.;N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-6.2
.;D
REVEL
Uncertain
0.63
Sift
Benign
0.063
.;T
Sift4G
Benign
0.069
T;T
Polyphen
0.91
.;P
Vest4
0.88
MutPred
0.60
Loss of catalytic residue at G155 (P = 0.0958);Loss of catalytic residue at G155 (P = 0.0958);
MVP
0.61
MPC
1.3
ClinPred
0.95
D
GERP RS
4.7
Varity_R
0.80
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1219408; API