rs864622118

chr19-1223095-T-Achr19-1223095-T-Cchr19-1223095-T-G

Variant summary

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

The NM_000455.5(STK11):c.1031T>A(p.Leu344Gln) 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. L344P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71

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, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.1031T>A	p.Leu344Gln	missense_variant	8/10	ENST00000326873.12
STK11	NM_001407255.1	c.1031T>A	p.Leu344Gln	missense_variant	8/9
STK11	NR_176325.1	n.2298T>A		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.1031T>A	p.Leu344Gln	missense_variant	8/10	1	NM_000455.5	P1

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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.36	T;D
Eigen	Benign	0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.51	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.64	T
Sift4G	Uncertain	0.047	D;T
Polyphen		0.66	.;P
Vest4		0.80
MutPred		0.46		Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);
MVP		0.66
MPC		0.30
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.36
gMVP		0.62

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: chr19-1223094;