rs730881973

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate

The NM_000455.5(STK11):​c.543C>A​(p.Asn181Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

STK11
NM_000455.5 missense

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38
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 Pathogenic. Variant got 10 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, 0.988
PP5
Variant 19-1220451-C-A is Pathogenic according to our data. Variant chr19-1220451-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3383208.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STK11NM_000455.5 linkuse as main transcriptc.543C>A p.Asn181Lys missense_variant 4/10 ENST00000326873.12 NP_000446.1
STK11NM_001407255.1 linkuse as main transcriptc.543C>A p.Asn181Lys missense_variant 4/9 NP_001394184.1
STK11NR_176325.1 linkuse as main transcriptn.1810C>A non_coding_transcript_exon_variant 5/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.543C>A p.Asn181Lys missense_variant 4/101 NM_000455.5 ENSP00000324856 P1Q15831-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;D;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Pathogenic
0.71
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Pathogenic
3.0
.;M;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-6.0
.;D;.
REVEL
Pathogenic
0.83
Sift
Pathogenic
0.0
.;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.98
MutPred
0.95
Gain of methylation at N181 (P = 0.0175);Gain of methylation at N181 (P = 0.0175);.;
MVP
0.95
MPC
2.3
ClinPred
1.0
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Varity_R
0.99
gMVP
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs730881973; hg19: chr19-1220450; API