19-1223091-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000455.5(STK11):​c.1027G>T​(p.Asp343Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

STK11
NM_000455.5 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STK11NM_000455.5 linkuse as main transcriptc.1027G>T p.Asp343Tyr missense_variant 8/10 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkuse as main transcriptc.1027G>T p.Asp343Tyr missense_variant 8/9 NP_001394184.1
STK11NR_176325.1 linkuse as main transcriptn.2294G>T non_coding_transcript_exon_variant 9/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.1027G>T p.Asp343Tyr missense_variant 8/101 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkuse as main transcriptc.1027G>T p.Asp343Tyr missense_variant 8/9 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkuse as main transcriptc.655G>T p.Asp219Tyr missense_variant 10/123 ENSP00000477641.2 A0A087WT72

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Melanoma, cutaneous malignant, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsNov 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
29
DANN
Uncertain
0.98
DEOGEN2
Benign
0.41
T;D
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.61
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Benign
2.0
.;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.015
.;D
Sift4G
Uncertain
0.035
D;D
Polyphen
0.98
.;D
Vest4
0.88
MutPred
0.45
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP
0.63
MPC
0.31
ClinPred
0.97
D
GERP RS
2.8
Varity_R
0.37
gMVP
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368547224; hg19: chr19-1223090; API