chr19-1207031-C-T

Position:

• chr19-1207031-C-T

Variant summary

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

The NM_000455.5(STK11):​c.118C>T​(p.Arg40Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51

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 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.118C>T	p.Arg40Cys	missense_variant	1/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.118C>T	p.Arg40Cys	missense_variant	1/9		NP_001394184.1
STK11	NR_176325.1	n.1254C>T		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.118C>T	p.Arg40Cys	missense_variant	1/10	1	NM_000455.5	ENSP00000324856	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;D;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	1.8	.;L;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-4.1	.;D;.
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	.;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.70
MutPred		0.57		Loss of MoRF binding (P = 0.004);Loss of MoRF binding (P = 0.004);Loss of MoRF binding (P = 0.004);
MVP		0.86
MPC		2.1
ClinPred		0.99	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.81

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: chr19-1207030;