19-1218442-C-G

Position:

• chr19-1218442-C-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.316C>G​(p.Arg106Gly) 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: 4.57

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, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.316C>G	p.Arg106Gly	missense_variant	2/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.316C>G	p.Arg106Gly	missense_variant	2/9		NP_001394184.1
STK11	NR_176325.1	n.1583C>G		non_coding_transcript_exon_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.316C>G	p.Arg106Gly	missense_variant	2/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.316C>G	p.Arg106Gly	missense_variant	2/9			ENSP00000498804.1
STK11	ENST00000585748	c.-57C>G		5_prime_UTR_variant	4/12	3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*141C>G		non_coding_transcript_exon_variant	3/4	3		ENSP00000466610.1
STK11	ENST00000593219.5	n.*141C>G		3_prime_UTR_variant	3/4	3		ENSP00000466610.1

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	Benign	0.17
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	0.030
Eigen_PC	Benign	-0.0071
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Uncertain	0.41
Sift	Benign	0.050	.;D
Sift4G	Benign	0.15	T;T
Polyphen		0.80	.;P
Vest4		0.62
MutPred		0.47		Loss of stability (P = 0.0215);Loss of stability (P = 0.0215);
MVP		0.69
MPC		1.7
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.66
gMVP		0.44

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: chr19-1218441;