rs59912467

Positions:

• chr19-1223126-C-A
• chr19-1223126-C-G
• chr19-1223126-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000455.5(STK11):​c.1062C>A​(p.Phe354Leu) 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32116854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1062C>A	p.Phe354Leu	missense_variant	8/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1062C>A	p.Phe354Leu	missense_variant	8/9		NP_001394184.1
STK11	NR_176325.1	n.2329C>A		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1062C>A	p.Phe354Leu	missense_variant	8/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.1062C>A	p.Phe354Leu	missense_variant	8/9			ENSP00000498804.1
STK11	ENST00000585748.3	c.690C>A	p.Phe230Leu	missense_variant	10/12	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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.085
DANN	Benign	0.61
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.20
Sift	Benign	0.24	.;T
Sift4G	Benign	0.57	T;T
Polyphen		0.062	.;B
Vest4		0.32
MutPred		0.79		Loss of stability (P = 0.0714);Loss of stability (P = 0.0714);
MVP		0.38
MPC		0.046
ClinPred		0.31	T
GERP RS		-7.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.19

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: chr19-1223125;