chr20-45000494-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006282.5(STK4):c.934G>A(p.Val312Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,613,508 control chromosomes in the GnomAD database, including 68,167 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5555 hom., cov: 32)

Exomes 𝑓: 0.28 ( 62612 hom. )

Consequence

STK4
NM_006282.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.77

Publications

31 publications found

Variant links:

Genes affected

STK4 (HGNC:11408): (serine/threonine kinase 4) The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]

STK4 Gene-Disease associations (from GenCC):

combined immunodeficiency due to STK4 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

STK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019894838).

BP6

Variant 20-45000494-G-A is Benign according to our data. Variant chr20-45000494-G-A is described in ClinVar as Benign. ClinVar VariationId is 1169470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5 link	c.934G>A	p.Val312Met	missense_variant	Exon 8 of 11	ENST00000372806.8	NP_006273.1	Q13043-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8 link	c.934G>A	p.Val312Met	missense_variant	Exon 8 of 11	1	NM_006282.5	ENSP00000361892.3		Q13043-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38239

AN:

152034

Hom.:

5551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.263

AC:

65988

AN:

250956

AF XY:

0.273

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.284

AC:

415719

AN:

1461356

Hom.:

62612

Cov.:

AF XY:

0.287

AC XY:

208479

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.142

AC:

4738

AN:

33472

American (AMR)

AF:

0.154

AC:

6879

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10800

AN:

26112

East Asian (EAS)

AF:

0.0122

AC:

483

AN:

39696

South Asian (SAS)

AF:

0.282

AC:

24348

AN:

86212

European-Finnish (FIN)

AF:

0.393

AC:

20985

AN:

53364

Middle Eastern (MID)

AF:

0.348

AC:

2008

AN:

5766

European-Non Finnish (NFE)

AF:

0.295

AC:

328418

AN:

1111668

Other (OTH)

AF:

0.283

AC:

17060

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

16288

32577

48865

65154

81442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10478

20956

31434

41912

52390

<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:

0.251

AC:

38258

AN:

152152

Hom.:

5555

Cov.:

AF XY:

0.255

AC XY:

18935

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.147

AC:

6110

AN:

41528

American (AMR)

AF:

0.214

AC:

3276

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1435

AN:

3470

East Asian (EAS)

AF:

0.0154

AC:

AN:

5184

South Asian (SAS)

AF:

0.260

AC:

1255

AN:

4822

European-Finnish (FIN)

AF:

0.394

AC:

4147

AN:

10538

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20877

AN:

67990

Other (OTH)

AF:

0.283

AC:

597

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1411

2822

4233

5644

7055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.285

Hom.:

20006

Bravo

AF:

0.230

TwinsUK

AF:

0.295

AC:

1095

ALSPAC

AF:

0.297

AC:

1146

ESP6500AA

AF:

0.153

AC:

674

ESP6500EA

AF:

0.312

AC:

2684

ExAC

AF:

0.264

AC:

31999

Asia WGS

AF:

0.135

AC:

473

AN:

3478

EpiCase

AF:

0.316

EpiControl

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined immunodeficiency due to STK4 deficiency

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;.

Eigen

Benign

0.022

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;L

PhyloP100

2.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.12

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.080

MPC

0.31

ClinPred

0.0069

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.30

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over