19-1220615-G-T

Position:

• chr19-1220615-G-T

Variant summary

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

The NM_000455.5(STK11):​c.632G>T​(p.Arg211Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.00

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.632G>T	p.Arg211Leu	missense_variant	5/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.632G>T	p.Arg211Leu	missense_variant	5/9		NP_001394184.1
STK11	NR_176325.1	n.1899G>T		non_coding_transcript_exon_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.632G>T	p.Arg211Leu	missense_variant	5/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.632G>T	p.Arg211Leu	missense_variant	5/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.260G>T	p.Arg87Leu	missense_variant	7/12	3		ENSP00000477641.2

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	Benign	0.22
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	31
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.68	.;N;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	.;N;.
REVEL	Uncertain	0.49
Sift	Benign	0.65	.;T;.
Sift4G	Benign	0.61	T;T;D
Polyphen		0.012	.;B;.
Vest4		0.84
MutPred		0.47		Loss of disorder (P = 0.0369);Loss of disorder (P = 0.0369);.;
MVP		0.94
MPC		1.5
ClinPred		0.89	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: 29

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: chr19-1220614;