rs587782267

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_000455.5(STK11):c.998G>A(p.Arg333His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R333C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

STK11
NM_000455.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 7.66

Publications

4 publications found

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]

STK11 Gene-Disease associations (from GenCC):

familial pancreatic carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Peutz-Jeghers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

STK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STK11	NM_000455.5	MANE Select	c.998G>A	p.Arg333His	missense	Exon 8 of 10	NP_000446.1
STK11	NM_001407255.1		c.998G>A	p.Arg333His	missense	Exon 8 of 9	NP_001394184.1
STK11	NR_176325.1		n.2265G>A		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STK11	ENST00000326873.12	TSL:1 MANE Select	c.998G>A	p.Arg333His	missense	Exon 8 of 10	ENSP00000324856.6
STK11	ENST00000652231.1		c.998G>A	p.Arg333His	missense	Exon 8 of 9	ENSP00000498804.1
STK11	ENST00000585748.3	TSL:3	c.626G>A	p.Arg209His	missense	Exon 10 of 12	ENSP00000477641.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453426

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

43784

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25942

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.00

AC:

AN:

84806

European-Finnish (FIN)

AF:

0.0000194

AC:

AN:

51572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108744

Other (OTH)

AF:

0.00

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peutz-Jeghers syndrome (2)

Hereditary cancer-predisposing syndrome (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

2.0

PhyloP100

7.7

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.51

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.86

Vest4

0.75

MutPred

0.47

Loss of helix (P = 0.0068)

MVP

0.72

MPC

0.32

ClinPred

0.96

GERP RS

3.8

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.36

gMVP

0.64

Mutation Taster

=30/70

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over