Variant 19-1221243-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_000455.5(STK11):c.765C>A(p.Phe255Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F255V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

STK11
NM_000455.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a domain Protein kinase (size 260) in uniprot entity STK11_HUMAN there are 89 pathogenic changes around while only 17 benign (84%) in NM_000455.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STK11	NM_000455.5 linkuse as main transcript	c.765C>A	p.Phe255Leu	missense_variant	6/10	ENST00000326873.12
STK11	NM_001407255.1 linkuse as main transcript	c.765C>A	p.Phe255Leu	missense_variant	6/9
STK11	NR_176325.1 linkuse as main transcript	n.2032C>A		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12 linkuse as main transcript	c.765C>A	p.Phe255Leu	missense_variant	6/10	1	NM_000455.5	P1	Q15831-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;D

Eigen

Benign

0.014

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.91

D;D

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.4

.;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.049

D;D

Polyphen

1.0

.;D

Vest4

0.95

MutPred

0.90

Gain of catalytic residue at F255 (P = 0.0184);Gain of catalytic residue at F255 (P = 0.0184);

MVP

0.93

MPC

1.6

ClinPred

1.0

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over