rs6073604

Variant names:

• chr20-45023486-G-A
• rs6073604
• NM_006282.5:c.1148-1487G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006282.5(STK4):​c.1148-1487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,138 control chromosomes in the GnomAD database, including 58,075 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58075 hom., cov: 30)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 3 publications found

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, ClinGen, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006282.5. 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
	STK4	NM_006282.5	MANE Select	c.1148-1487G>A		intron	N/A	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.1148-1487G>A		intron	N/A	NP_001339314.1	Q13043-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.1148-1487G>A		intron	N/A	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.983-1487G>A		intron	N/A	ENSP00000443514.1	F5H5B4
	STK4	ENST00000372801.5	TSL:2	c.1148-1487G>A		intron	N/A	ENSP00000361887.1	Q13043-2

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132653 AN: 152020 Hom.: 58021 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.864

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132767 AN: 152138 Hom.: 58075 Cov.: 30 AF XY: 0.876 AC XY: 65201 AN XY: 74390

African (AFR) AF: 0.906 AC: 37599 AN: 41492

American (AMR) AF: 0.865 AC: 13219 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2774 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4984 AN: 5172

South Asian (SAS) AF: 0.888 AC: 4286 AN: 4824

European-Finnish (FIN) AF: 0.914 AC: 9681 AN: 10590

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57350 AN: 67986

Other (OTH) AF: 0.866 AC: 1830 AN: 2114

Alfa AF: 0.850 Hom.: 87156

Bravo AF: 0.872

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.5
DANN	Benign	0.69
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6073604; hg19: chr20-43652127;