chr20-44998055-T-C

Variant names:

• chr20-44998055-T-C
• rs7271519
• NM_006282.5:c.831+749T>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.831+749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,072 control chromosomes in the GnomAD database, including 5,688 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 0.26 (5688 hom., cov: 32)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 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.831+749T>C		intron	N/A	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.831+749T>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.831+749T>C		intron	N/A	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.666+749T>C		intron	N/A	ENSP00000443514.1	F5H5B4
	STK4	ENST00000372801.5	TSL:2	c.831+749T>C		intron	N/A	ENSP00000361887.1	Q13043-2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38985 AN: 151954 Hom.: 5684 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.256 AC: 39004 AN: 152072 Hom.: 5688 Cov.: 32 AF XY: 0.260 AC XY: 19289 AN XY: 74330

African (AFR) AF: 0.162 AC: 6733 AN: 41482

American (AMR) AF: 0.217 AC: 3319 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3472

East Asian (EAS) AF: 0.0156 AC: 81 AN: 5184

South Asian (SAS) AF: 0.261 AC: 1258 AN: 4822

European-Finnish (FIN) AF: 0.395 AC: 4174 AN: 10560

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20908 AN: 67958

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.297 Hom.: 11453

Bravo AF: 0.236

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		-0.027
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: rs7271519; hg19: chr20-43626696;