Genetic Variant STK39:p.Lys404Lys (chr2-168075109-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_013233.3(STK39):c.1212G>A(p.Lys404Lys) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000343 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

STK39
NM_013233.3 splice_region, synonymous

Scores

Splicing: ADA: 0.9996

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86

Publications

4 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: Likely_benign. The variant received -3 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BS2

High AC in GnomAd4 at 210 AD gene.

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.1212G>A	p.Lys404Lys	splice_region synonymous	Exon 11 of 18	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.1212G>A	p.Lys404Lys	splice_region synonymous	Exon 11 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.1212G>A	p.Lys404Lys	splice_region synonymous	Exon 11 of 18	ENSP00000348278.4	Q9UEW8-1
STK39	ENST00000487143.5	TSL:1	n.312G>A		splice_region non_coding_transcript_exon	Exon 2 of 9
STK39	ENST00000952313.1		c.1212G>A	p.Lys404Lys	splice_region synonymous	Exon 11 of 19	ENSP00000622372.1

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.000103

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.000345

AC:

AN:

249488

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000235

AC:

343

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00544

AC:

182

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000953

AC:

106

AN:

1112004

Other (OTH)

AF:

0.000530

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00138

AC:

210

AN:

152278

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00428

AC:

178

AN:

41542

American (AMR)

AF:

0.00131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000404

Hom.:

Bravo

AF:

0.00163

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

4.9

Mutation Taster

=0/100

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over