rs6073627

Variant names:

• chr20-45076910-C-G
• rs6073627
• NM_006282.5:c.*1734C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006282.5(STK4):​c.*1734C>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 0.124 in 152,210 control chromosomes in the GnomAD database, including 1,542 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 0.12 (1542 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK4 NM_006282.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• 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, ClinGen, Orphanet, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 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.*1734C>G		3_prime_UTR	Exon 11 of 11	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.*1904C>G		3_prime_UTR	Exon 12 of 12	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.*1734C>G		3_prime_UTR	Exon 11 of 11	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.*1734C>G		3_prime_UTR	Exon 10 of 10	ENSP00000443514.1	F5H5B4
	STK4	ENST00000925605.1		c.*1734C>G		3_prime_UTR	Exon 10 of 10	ENSP00000595664.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18924 AN: 152090 Hom.: 1544 Cov.: 32

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.118

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.124 AC: 18921 AN: 152210 Hom.: 1542 Cov.: 32 AF XY: 0.123 AC XY: 9166 AN XY: 74410

African (AFR) AF: 0.0369 AC: 1533 AN: 41552

American (AMR) AF: 0.0893 AC: 1367 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5170

South Asian (SAS) AF: 0.108 AC: 523 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1968 AN: 10568

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11746 AN: 68002

Other (OTH) AF: 0.120 AC: 253 AN: 2108

Alfa AF: 0.146 Hom.: 226

Bravo AF: 0.117

Asia WGS AF: 0.182 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.67
PhyloP100		0.84
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: rs6073627; hg19: chr20-43705551;