dbSNP rs587782468: STK11:p.Ala205Glu (chr19-1220597-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_000455.5(STK11):c.614C>A(p.Ala205Glu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A205T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STK11
NM_000455.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.80

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]

STK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a domain Protein kinase (size 260) in uniprot entity STK11_HUMAN there are 93 pathogenic changes around while only 28 benign (77%) in NM_000455.5

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5 link	c.614C>A	p.Ala205Glu	missense_variant	Exon 5 of 10	ENST00000326873.12	NP_000446.1	Q15831-1A0A0S2Z4D1
STK11	NM_001407255.1 link	c.614C>A	p.Ala205Glu	missense_variant	Exon 5 of 9		NP_001394184.1
STK11	NR_176325.1 link	n.1881C>A		non_coding_transcript_exon_variant	Exon 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK11	ENST00000326873.12 link	c.614C>A	p.Ala205Glu	missense_variant	Exon 5 of 10	1	NM_000455.5	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1 link	c.614C>A	p.Ala205Glu	missense_variant	Exon 5 of 9			ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3 link	c.242C>A	p.Ala81Glu	missense_variant	Exon 7 of 12	3		ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713142

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

32972

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

41472

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25540

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

38546

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

83786

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

50154

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

1100516

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

59294

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.28

T;T;T

Eigen

Benign

0.046

Eigen_PC

Benign

0.077

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.015

.;N;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.9

.;D;.

REVEL

Uncertain

0.34

Sift

Benign

0.035

.;D;.

Sift4G

Benign

0.49

T;T;T

Polyphen

0.86

.;P;.

Vest4

0.77

MutPred

0.36

Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);.;

MVP

0.75

MPC

2.3

ClinPred

0.94

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.94

Mutation Taster

=30/70

disease causing

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over