19-1223110-A-T

Position:

• chr19-1223110-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000326873.12(STK11):​c.1046A>T​(p.Glu349Val) 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. 16/21 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. E349K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 ENST00000326873.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1446161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.1046A>T	p.Glu349Val	missense_variant	8/10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.1046A>T	p.Glu349Val	missense_variant	8/9		NP_001394184.1
STK11	NR_176325.1	n.2313A>T		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.1046A>T	p.Glu349Val	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	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.32	T;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.17
Sift	Benign	0.18	.;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0040	.;B
Vest4		0.13
MutPred		0.50		Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);
MVP		0.61
MPC		0.046
ClinPred		0.15	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.45

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: chr19-1223109;