rs1555738370

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000455.5(STK11):​c.620A>C​(p.Asp207Ala) variant causes a missense change involving the alteration of a 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. D207D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

STK11
NM_000455.5 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.36
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a domain Protein kinase (size 260) in uniprot entity STK11_HUMAN there are 19 pathogenic changes around while only 5 benign (79%) in NM_000455.5
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STK11NM_000455.5 linkuse as main transcriptc.620A>C p.Asp207Ala missense_variant 5/10 ENST00000326873.12 NP_000446.1
STK11NM_001407255.1 linkuse as main transcriptc.620A>C p.Asp207Ala missense_variant 5/9 NP_001394184.1
STK11NR_176325.1 linkuse as main transcriptn.1887A>C non_coding_transcript_exon_variant 6/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.620A>C p.Asp207Ala missense_variant 5/101 NM_000455.5 ENSP00000324856 P1Q15831-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.31
T;D;T
Eigen
Benign
-0.015
Eigen_PC
Benign
0.044
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.4
.;L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-4.8
.;D;.
REVEL
Uncertain
0.34
Sift
Uncertain
0.0080
.;D;.
Sift4G
Benign
0.085
T;T;D
Polyphen
0.52
.;P;.
Vest4
0.71
MutPred
0.56
Gain of catalytic residue at D207 (P = 0.0747);Gain of catalytic residue at D207 (P = 0.0747);.;
MVP
0.69
MPC
1.6
ClinPred
0.94
D
GERP RS
5.6
Varity_R
0.65
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: chr19-1220602; API