NM_006282.5:c.526-73C>A

Variant names:

• chr20-44995017-C-A
• rs6017460
• NM_006282.5:c.526-73C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006282.5(STK4):​c.526-73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 917,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 27)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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.526-73C>A		intron	N/A	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.526-73C>A		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.526-73C>A		intron	N/A	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.361-73C>A		intron	N/A	ENSP00000443514.1	F5H5B4
	STK4	ENST00000372801.5	TSL:2	c.526-73C>A		intron	N/A	ENSP00000361887.1	Q13043-2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.000453 AC: 415 AN: 917120 Hom.: 0 AF XY: 0.000527 AC XY: 236 AN XY: 447436

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000733 AC: 14 AN: 19094

American (AMR) AF: 0.00125 AC: 20 AN: 15968

Ashkenazi Jewish (ASJ) AF: 0.00134 AC: 18 AN: 13420

East Asian (EAS) AF: 0.00176 AC: 43 AN: 24444

South Asian (SAS) AF: 0.000355 AC: 9 AN: 25362

European-Finnish (FIN) AF: 0.000850 AC: 30 AN: 35288

Middle Eastern (MID) AF: 0.000271 AC: 1 AN: 3690

European-Non Finnish (NFE) AF: 0.000345 AC: 256 AN: 742848

Other (OTH) AF: 0.000649 AC: 24 AN: 37006

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.43
PhyloP100		-2.2

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: rs6017460; hg19: chr20-43623658;