19-1207028-C-A

Position:

• chr19-1207028-C-A

Variant summary

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

The ENST00000326873.12(STK11):​c.115C>A​(p.Arg39Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK11 ENST00000326873.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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]

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.115C>A	p.Arg39Ser	missense_variant	1/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.115C>A	p.Arg39Ser	missense_variant	1/9		NP_001394184.1
STK11	NR_176325.1	n.1251C>A		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.115C>A	p.Arg39Ser	missense_variant	1/10	1	NM_000455.5	ENSP00000324856	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2021

Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;D;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	0.0084	D
MutationAssessor	Uncertain	2.2	.;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.2	.;N;.
REVEL	Uncertain	0.60
Sift	Uncertain	0.013	.;D;.
Sift4G	Uncertain	0.021	D;D;T
Polyphen		0.92	.;P;.
Vest4		0.65
MutPred		0.42		Gain of phosphorylation at R39 (P = 0.036);Gain of phosphorylation at R39 (P = 0.036);Gain of phosphorylation at R39 (P = 0.036);
MVP		0.86
MPC		2.2
ClinPred		0.95	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.90

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: chr19-1207027;