NM_006282.5:c.1306-3354G>C

Variant names:

• chr20-45071664-G-C
• rs10485454
• NM_006282.5:c.1306-3354G>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.1306-3354G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,194 control chromosomes in the GnomAD database, including 1,322 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 0.11 (1322 hom., cov: 32)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	NM_006282.5	MANE Select	c.1306-3354G>C		intron	N/A	NP_006273.1
	STK4	NM_001352385.2		c.*12-3354G>C		intron	N/A	NP_001339314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.1306-3354G>C		intron	N/A	ENSP00000361892.3
	STK4	ENST00000499879.8	TSL:1	c.1141-3354G>C		intron	N/A	ENSP00000443514.1
	STK4	ENST00000372801.5	TSL:2	c.*12-3354G>C		intron	N/A	ENSP00000361887.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17403 AN: 152076 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.114 AC: 17409 AN: 152194 Hom.: 1322 Cov.: 32 AF XY: 0.116 AC XY: 8646 AN XY: 74420

African (AFR) AF: 0.0269 AC: 1119 AN: 41544

American (AMR) AF: 0.110 AC: 1675 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.129 AC: 621 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1976 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 57 AN: 290

European-Non Finnish (NFE) AF: 0.159 AC: 10828 AN: 67992

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.0845 Hom.: 109

Bravo AF: 0.101

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.5
DANN	Benign	0.70
PhyloP100		1.3
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: rs10485454; hg19: chr20-43700305;