19-1207084-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.171A>T(p.Glu57Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. E57E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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 region_of_interest Sufficient for interaction with SIRT1 (size 45) in uniprot entity STK11_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) 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.171A>T	p.Glu57Asp	missense_variant	1/10	ENST00000326873.12
STK11	NM_001407255.1	c.171A>T	p.Glu57Asp	missense_variant	1/9
STK11	NR_176325.1	n.1307A>T		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.171A>T	p.Glu57Asp	missense_variant	1/10	1	NM_000455.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.61	.;P;.
Vest4		0.67
MutPred		0.30		Gain of ubiquitination at K62 (P = 0.123);Gain of ubiquitination at K62 (P = 0.123);Gain of ubiquitination at K62 (P = 0.123);
MVP		0.74
MPC		2.0
ClinPred		0.97	D
GERP RS		0.0048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.48

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: chr19-1207083;