19-1223095-T-G

Position:

• chr19-1223095-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000455.5(STK11):​c.1031T>G​(p.Leu344Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 7.71

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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1031T>G	p.Leu344Arg	missense_variant	8/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1031T>G	p.Leu344Arg	missense_variant	8/9		NP_001394184.1
STK11	NR_176325.1	n.2298T>G		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1031T>G	p.Leu344Arg	missense_variant	8/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.1031T>G	p.Leu344Arg	missense_variant	8/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.659T>G	p.Leu220Arg	missense_variant	10/12	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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T;D
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	.;N
REVEL	Uncertain	0.52
Sift	Benign	0.067	.;T
Sift4G	Uncertain	0.053	T;T
Polyphen		0.97	.;D
Vest4		0.84
MutPred		0.54		Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);
MVP		0.57
MPC		0.33
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.38
gMVP		0.75

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: chr19-1223094;