chr19-1223100-G-C

Variant names:

• chr19-1223100-G-C
• NM_000455.5:c.1036G>C

Variant summary

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

The NM_000455.5(STK11):​c.1036G>C​(p.Gly346Arg) 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: 6.51

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, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.1036G>C	p.Gly346Arg	missense_variant	Exon 8 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1036G>C	p.Gly346Arg	missense_variant	Exon 8 of 9		NP_001394184.1
STK11	NR_176325.1	n.2303G>C		non_coding_transcript_exon_variant	Exon 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1036G>C	p.Gly346Arg	missense_variant	Exon 8 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.1036G>C	p.Gly346Arg	missense_variant	Exon 8 of 9			ENSP00000498804.1
STK11	ENST00000585748.3	c.664G>C	p.Gly222Arg	missense_variant	Exon 10 of 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;D
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	.;N
REVEL	Uncertain	0.30
Sift	Benign	0.088	.;T
Sift4G	Benign	0.074	T;T
Polyphen		1.0	.;D
Vest4		0.66
MutPred		0.48		Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);
MVP		0.68
MPC		0.29
ClinPred		0.89	D
GERP RS		1.6
Varity_R		0.090
gMVP		0.59

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: chr19-1223099;