20-45079656-T-G

Variant names:

• chr20-45079656-T-G
• rs8000
• NM_006282.5:c.*4480T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006282.5(STK4):​c.*4480T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,468 control chromosomes in the GnomAD database, including 22,416 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 0.53 (22331 hom., cov: 32)
  • Exomes 𝑓: 0.61 (85 hom.)
• Consequence: STK4 NM_006282.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 9 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, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.*4480T>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.*4480T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_006282.5	ENSP00000361892.3
STK4	ENST00000499879.8	c.*4480T>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000443514.1
STK4	ENST00000474717.3	c.*4480T>G		3_prime_UTR_variant	Exon 11 of 11	3		ENSP00000479564.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80315 AN: 151918 Hom.: 22289 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.609 AC: 263 AN: 432 Hom.: 85 Cov.: 0 AF XY: 0.619 AC XY: 161 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.608 AC: 259 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.529 AC: 80411 AN: 152036 Hom.: 22331 Cov.: 32 AF XY: 0.527 AC XY: 39196 AN XY: 74320

African (AFR) AF: 0.682 AC: 28276 AN: 41466

American (AMR) AF: 0.369 AC: 5646 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1737 AN: 5174

South Asian (SAS) AF: 0.382 AC: 1844 AN: 4830

European-Finnish (FIN) AF: 0.600 AC: 6308 AN: 10520

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33123 AN: 67976

Other (OTH) AF: 0.529 AC: 1118 AN: 2112

Alfa AF: 0.499 Hom.: 17841

Bravo AF: 0.517

Asia WGS AF: 0.411 AC: 1431 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs8000; hg19: chr20-43708297; COSMIC: COSV65670235; COSMIC: COSV65670235;