rs4810446

Positions:

• chr20-44967227-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
STK4	NM_006282.5	c.35+624T>A		intron_variant		ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.35+624T>A		intron_variant		1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13784 AN: 152048 Hom.: 754 Cov.: 32

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.: 29 AF XY: 0.0793 AC XY: 30495 AN XY: 384644

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.: 32 AF XY: 0.0946 AC XY: 7037 AN XY: 74388

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.: 82

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Other links and lift over

dbSNP: rs4810446; hg19: chr20-43595868;