rs751619208

Positions:

• chr19-1223099-C-G
• chr19-1223099-C-T

Variant summary

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

The NM_000455.5(STK11):​c.1035C>G​(p.His345Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1035C>G	p.His345Gln	missense_variant	8/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1035C>G	p.His345Gln	missense_variant	8/9		NP_001394184.1
STK11	NR_176325.1	n.2302C>G		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1035C>G	p.His345Gln	missense_variant	8/10	1	NM_000455.5	ENSP00000324856	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	0.84
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T;D
Eigen	Benign	0.025
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	2.0	.;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.8	.;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	.;D
Vest4		0.65
MutPred		0.42		Gain of disorder (P = 0.099);Gain of disorder (P = 0.099);
MVP		0.69
MPC		0.29
ClinPred		1.0	D
GERP RS		-0.037
Varity_R		0.45
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr19-1223098;