Genetic Variant NM_013233.3:c.190G>A (chr2-168247246-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013233.3(STK39):c.190G>A(p.Glu64Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 1,153,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 9.9e-7 ( 0 hom. )

Consequence

STK39
NM_013233.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

0 publications found

Variant links:

Genes affected

STK39 (HGNC:17717): (serine/threonine kinase 39) This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress. [provided by RefSeq, Jul 2008]

STK39 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013233.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	NM_013233.3	MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 1 of 18	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.190G>A	p.Glu64Lys	missense	Exon 1 of 17	NP_001397890.1	A0A8V8TKT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK39	ENST00000355999.5	TSL:1 MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 1 of 18	ENSP00000348278.4	Q9UEW8-1
STK39	ENST00000952313.1		c.190G>A	p.Glu64Lys	missense	Exon 1 of 19	ENSP00000622372.1
STK39	ENST00000697205.1		c.190G>A	p.Glu64Lys	missense	Exon 1 of 17	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes

AF:

0.00000680

AC:

AN:

147062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000120

AC:

AN:

8318

AF XY:

0.000201

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

9.93e-7

AC:

AN:

1006710

Hom.:

Cov.:

AF XY:

0.00000206

AC XY:

AN XY:

484324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19658

American (AMR)

AF:

0.00

AC:

AN:

6722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10492

East Asian (EAS)

AF:

0.00

AC:

AN:

18354

South Asian (SAS)

AF:

0.00

AC:

AN:

28142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2402

European-Non Finnish (NFE)

AF:

0.00000115

AC:

AN:

871742

Other (OTH)

AF:

0.00

AC:

AN:

36914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000680

AC:

AN:

147062

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71626

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40656

American (AMR)

AF:

0.00

AC:

AN:

14872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4984

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66292

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

-0.11

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.59

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.73

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

PhyloP100

2.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.29

Sift

Benign

0.32

Sift4G

Benign

0.32

Polyphen

0.29

Vest4

0.32

MutPred

0.55

Gain of MoRF binding (P = 0.0101)

MVP

0.44

MPC

1.4

ClinPred

0.11

GERP RS

4.3

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.47

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over