chr19-1206969-C-G

Position:

• chr19-1206969-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000455.5(STK11):​c.56C>G​(p.Ser19Trp) 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: 32)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.16

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 2 ACMG points.

• 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.56C>G	p.Ser19Trp	missense_variant	1/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.56C>G	p.Ser19Trp	missense_variant	1/9		NP_001394184.1
STK11	NR_176325.1	n.1192C>G		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.56C>G	p.Ser19Trp	missense_variant	1/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.56C>G	p.Ser19Trp	missense_variant	1/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.-82-11448C>G		intron_variant		3		ENSP00000477641.2
STK11	ENST00000593219.5	n.56C>G		non_coding_transcript_exon_variant	1/4	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;D;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.95	.;N;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	.;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.98	.;D;.
Vest4		0.54
MutPred		0.45		Gain of catalytic residue at L17 (P = 0.0125);Gain of catalytic residue at L17 (P = 0.0125);Gain of catalytic residue at L17 (P = 0.0125);
MVP		0.64
MPC		2.2
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.42
gMVP		0.50

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: chr19-1206968;