19-1207029-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000455.5(STK11):c.116G>C(p.Arg39Pro) 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. 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 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.45

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.116G>C	p.Arg39Pro	missense_variant	1/10	ENST00000326873.12
STK11	NM_001407255.1	c.116G>C	p.Arg39Pro	missense_variant	1/9
STK11	NR_176325.1	n.1252G>C		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.116G>C	p.Arg39Pro	missense_variant	1/10	1	NM_000455.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Pathogenic	28
Dann	Uncertain	0.99
DEOGEN2	Benign	0.35	T;D;T
Eigen	Benign	0.029
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	-0.076	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.91	D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.14	.;B;.
Vest4		0.67
MutPred		0.54		Gain of glycosylation at R39 (P = 0.0053);Gain of glycosylation at R39 (P = 0.0053);Gain of glycosylation at R39 (P = 0.0053);
MVP		0.86
MPC		2.5
ClinPred		0.98	D
GERP RS		2.7
Varity_R		0.67
gMVP		0.94

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: chr19-1207028;