rs1555738722

Positions:

• chr19-1221322-C-A
• chr19-1221322-C-G
• chr19-1221322-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000455.5(STK11):​c.844C>A​(p.Leu282Ile) variant causes a missense change. 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)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96

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 5 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, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.844C>A	p.Leu282Ile	missense_variant	6/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.844C>A	p.Leu282Ile	missense_variant	6/9		NP_001394184.1
STK11	NR_176325.1	n.2111C>A		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.844C>A	p.Leu282Ile	missense_variant	6/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.844C>A	p.Leu282Ile	missense_variant	6/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.472C>A	p.Leu158Ile	missense_variant	8/12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	.;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.025	.;D
Sift4G	Benign	0.11	T;T
Polyphen		0.37	.;B
Vest4		0.66
MutPred		0.56		Loss of ubiquitination at K287 (P = 0.0834);Loss of ubiquitination at K287 (P = 0.0834);
MVP		0.50
MPC		0.20
ClinPred		0.92	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.71
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1221321;