rs17322289

Positions:

• chr20-44971310-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006282.5(STK4):​c.36-768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,256 control chromosomes in the GnomAD database, including 612 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 0.072 (612 hom., cov: 31)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5	c.36-768T>C		intron_variant		ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8	c.36-768T>C		intron_variant		1	NM_006282.5	P1

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10999 AN: 152138 Hom.: 612 Cov.: 31

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0722 AC: 10998 AN: 152256 Hom.: 612 Cov.: 31 AF XY: 0.0692 AC XY: 5154 AN XY: 74428

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0981 Hom.: 1073

Bravo AF: 0.0670

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs17322289; hg19: chr20-43599951;