rs587780011

chr19-1221961-A-Cchr19-1221961-A-Gchr19-1221961-A-T

Variant summary

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

The NM_000455.5(STK11):c.875A>C(p.Tyr292Ser) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y292C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60

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 hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 3 benign, 12 uncertain in NM_000455.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.875A>C	p.Tyr292Ser	missense_variant	7/10	ENST00000326873.12
STK11	NM_001407255.1	c.875A>C	p.Tyr292Ser	missense_variant	7/9
STK11	NR_176325.1	n.2142A>C		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.875A>C	p.Tyr292Ser	missense_variant	7/10	1	NM_000455.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
Cadd	Uncertain	24
Dann	Benign	0.83
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.55	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.45	T;T
Polyphen		0.51	.;P
Vest4		0.62
MutPred		0.49		Gain of disorder (P = 0.0023);Gain of disorder (P = 0.0023);
MVP		0.97
MPC		0.31
ClinPred		0.62	D
GERP RS		3.6
Varity_R		0.36
gMVP		0.87

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: chr19-1221960;