rs16989639

Variant names:

• chr20-45051380-T-C
• rs16989639
• NM_006282.5:c.1306-23638T>C

Variant summary

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

The NM_006282.5(STK4):​c.1306-23638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 152,298 control chromosomes in the GnomAD database, including 183 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 0.028 (183 hom., cov: 32)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 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.1306-23638T>C		intron	N/A	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.1306-1706T>C		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.1306-23638T>C		intron	N/A	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.1141-23638T>C		intron	N/A	ENSP00000443514.1	F5H5B4
	STK4	ENST00000372801.5	TSL:2	c.1306-1706T>C		intron	N/A	ENSP00000361887.1	Q13043-2

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4252 AN: 152180 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0281 AC: 4277 AN: 152298 Hom.: 183 Cov.: 32 AF XY: 0.0277 AC XY: 2065 AN XY: 74484

African (AFR) AF: 0.0922 AC: 3832 AN: 41546

American (AMR) AF: 0.0116 AC: 178 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68026

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.0201 Hom.: 9

Bravo AF: 0.0303

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.061
DANN	Benign	0.52
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16989639; hg19: chr20-43680021;