STK4 p.Leu276Leu

Variant names:

• chr20-44997300-C-C
• ENST00000372806.8:c.

Your query was ambiguous. Multiple possible variants found:

• chr20-44997301--
• chr20-44997301-C-T
• chr20-44997303-G-T
• chr20-44997303-G-C
• chr20-44997303-G-A
• chr20-44997301-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000372806.8(STK4):​c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK4 ENST00000372806.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85
• Publications: 0 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372806.8. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.		intron	N/A	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.		intron	N/A	ENSP00000443514.1	F5H5B4
	STK4	ENST00000372801.5	TSL:2	c.		intron	N/A	ENSP00000361887.1	Q13043-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-43625941;