chr19-1219398-T-G

Position:

• chr19-1219398-T-G

Variant summary

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

The NM_000455.5(STK11):​c.449T>G​(p.Val150Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V150M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.449T>G	p.Val150Gly	missense_variant	3/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.449T>G	p.Val150Gly	missense_variant	3/9		NP_001394184.1
STK11	NR_176325.1	n.1716T>G		non_coding_transcript_exon_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.449T>G	p.Val150Gly	missense_variant	3/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.449T>G	p.Val150Gly	missense_variant	3/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.77T>G	p.Val26Gly	missense_variant	5/12	3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*274T>G		downstream_gene_variant		3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T;D
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.00082
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.7	.;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.020	.;D
Sift4G	Benign	0.35	T;T
Polyphen		0.34	.;B
Vest4		0.69
MutPred		0.44		Gain of disorder (P = 0.0376);Gain of disorder (P = 0.0376);
MVP		0.86
MPC		1.3
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.65
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-1219397;