19-1219386-A-T

Position:

• chr19-1219386-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000455.5(STK11):​c.437A>T​(p.Lys146Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.437A>T	p.Lys146Met	missense_variant	3/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.437A>T	p.Lys146Met	missense_variant	3/9		NP_001394184.1
STK11	NR_176325.1	n.1704A>T		non_coding_transcript_exon_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.437A>T	p.Lys146Met	missense_variant	3/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.437A>T	p.Lys146Met	missense_variant	3/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.65A>T	p.Lys22Met	missense_variant	5/12	3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*262A>T		downstream_gene_variant		3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;D
Eigen	Benign	0.12
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.1	.;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.86	.;P
Vest4		0.68
MutPred		0.52		Loss of solvent accessibility (P = 0.002);Loss of solvent accessibility (P = 0.002);
MVP		0.89
MPC		2.1
ClinPred		0.99	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-1219385;