Variant NM_006282.5:c.36-46C>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006282.5(STK4):c.36-46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,547,962 control chromosomes in the GnomAD database, including 175,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20040 hom., cov: 32)

Exomes 𝑓: 0.47 ( 155764 hom. )

Consequence

STK4
NM_006282.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.304

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 20-44972032-C-G is Benign according to our data. Variant chr20-44972032-C-G is described in ClinVar as [Benign]. Clinvar id is 1334913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5 link	c.36-46C>G		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.36-46C>G		intron_variant	Intron 1 of 10	1	NM_006282.5	ENSP00000361892.3		Q13043-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76441

AN:

151852

Hom.:

20003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.443

AC:

109470

AN:

247332

Hom.:

26051

AF XY:

0.447

AC XY:

59937

AN XY:

134108

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.466

AC:

650967

AN:

1395992

Hom.:

155764

Cov.:

AF XY:

0.465

AC XY:

325057

AN XY:

698330

show subpopulations

Gnomad4 AFR exome

AF:

0.605

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.569

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.504

AC:

76529

AN:

151970

Hom.:

20040

Cov.:

AF XY:

0.502

AC XY:

37272

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.502

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.485

Gnomad4 OTH

AF:

0.506

Alfa

AF:

0.495

Hom.:

3362

Bravo

AF:

0.490

Asia WGS

AF:

0.357

AC:

1247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. 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

- -

Combined immunodeficiency due to STK4 deficiency

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.58

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

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