19-1226627-T-G

Position:

• chr19-1226627-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000455.5(STK11):​c.1282T>G​(p.Ser428Ala) 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. Synonymous variant affecting the same amino acid position (i.e. S428S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96

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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and RPS6KA1 (size 0) in uniprot entity STK11_HUMAN
• 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.1282T>G	p.Ser428Ala	missense_variant	9/10	ENST00000326873.12	NP_000446.1
STK11	NR_176325.1	n.2549T>G		non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1282T>G	p.Ser428Ala	missense_variant	9/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000585748.3	c.910T>G	p.Ser304Ala	missense_variant	11/12	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	Benign	0.11
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.17
Sift	Benign	0.13	.;T
Sift4G	Uncertain	0.043	D;T
Polyphen		0.91	.;P
Vest4		0.55
MutPred		0.23		.;Loss of phosphorylation at S428 (P = 0.0026);
MVP		0.66
MPC		0.067
ClinPred		0.87	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.23

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: chr19-1226626;