19-1207123-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000455.5(STK11):c.210G>C(p.Glu70Asp) 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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E70G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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 2 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.18102142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.210G>C	p.Glu70Asp	missense_variant	1/10	ENST00000326873.12
STK11	NM_001407255.1	c.210G>C	p.Glu70Asp	missense_variant	1/9
STK11	NR_176325.1	n.1346G>C		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.210G>C	p.Glu70Asp	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	Benign	0.11
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.16
MutPred		0.23		Gain of MoRF binding (P = 0.1233);Gain of MoRF binding (P = 0.1233);Gain of MoRF binding (P = 0.1233);
MVP		0.74
MPC		0.90
ClinPred		0.39	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.50

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: chr19-1207122;