19-1206957-G-T

Position:

• chr19-1206957-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000455.5(STK11):​c.44G>T​(p.Gly15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1961394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.44G>T	p.Gly15Val	missense_variant	1/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.44G>T	p.Gly15Val	missense_variant	1/9		NP_001394184.1
STK11	NR_176325.1	n.1180G>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.44G>T	p.Gly15Val	missense_variant	1/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.44G>T	p.Gly15Val	missense_variant	1/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.-82-11460G>T		intron_variant		3		ENSP00000477641.2
STK11	ENST00000593219.5	n.44G>T		non_coding_transcript_exon_variant	1/4	3		ENSP00000466610.1

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	Benign	0.18
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.61	.;N;.
REVEL	Benign	0.075
Sift	Uncertain	0.0060	.;D;.
Sift4G	Uncertain	0.041	D;D;D
Polyphen		0.047	.;B;.
Vest4		0.15
MutPred		0.48		Loss of disorder (P = 0.0525);Loss of disorder (P = 0.0525);Loss of disorder (P = 0.0525);
MVP		0.44
MPC		1.3
ClinPred		0.70	D
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.46

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: chr19-1206956;