Variant 20-44967227-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006282.5(STK4):c.35+624T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 985,110 control chromosomes in the GnomAD database, including 3,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.091 ( 755 hom., cov: 32)

Exomes 𝑓: 0.079 ( 2763 hom. )

Consequence

STK4
NM_006282.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 20-44967227-T-A is Benign according to our data. Variant chr20-44967227-T-A is described in ClinVar as [Benign]. Clinvar id is 2688246.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5 link	c.35+624T>A		intron_variant	Intron 1 of 10	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.35+624T>A		intron_variant	Intron 1 of 10	1	NM_006282.5	ENSP00000361892.3		Q13043-1

Frequencies

GnomAD3 genomes

AF:

0.0907

AC:

13784

AN:

152048

Hom.:

754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0608

Gnomad FIN

AF:

0.0957

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.0793

AC:

66039

AN:

832944

Hom.:

2763

Cov.:

AF XY:

0.0793

AC XY:

30495

AN XY:

384644

show subpopulations

Gnomad4 AFR exome

AF:

0.0610

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.0633

Gnomad4 FIN exome

AF:

0.0652

Gnomad4 NFE exome

AF:

0.0784

Gnomad4 OTH exome

AF:

0.0936

GnomAD4 genome

AF:

0.0906

AC:

13791

AN:

152166

Hom.:

755

Cov.:

AF XY:

0.0946

AC XY:

7037

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0606

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.0615

Gnomad4 FIN

AF:

0.0957

Gnomad4 NFE

AF:

0.0808

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.0889

Hom.:

Bravo

AF:

0.0994

Asia WGS

AF:

0.114

AC:

396

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

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 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.8

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: 2

DS_DG_spliceai

0.20

Position offset: 44

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over