20-45077918-G-A

Variant names:

• chr20-45077918-G-A
• rs6073629
• NM_006282.5:c.*2742G>A

Variant summary

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

The NM_006282.5(STK4):​c.*2742G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,152 control chromosomes in the GnomAD database, including 1,769 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 0.14 (1769 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: 2.01
• Publications: 14 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=-0.51).
• 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.*2742G>A		3_prime_UTR	Exon 11 of 11	NP_006273.1	Q13043-1
	STK4	NM_001352385.2		c.*2912G>A		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.*2742G>A		3_prime_UTR	Exon 11 of 11	ENSP00000361892.3	Q13043-1
	STK4	ENST00000499879.8	TSL:1	c.*2742G>A		3_prime_UTR	Exon 10 of 10	ENSP00000443514.1	F5H5B4
	STK4	ENST00000925605.1		c.*2742G>A		3_prime_UTR	Exon 10 of 10	ENSP00000595664.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21804 AN: 152034 Hom.: 1768 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.138

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.143 AC: 21820 AN: 152152 Hom.: 1769 Cov.: 32 AF XY: 0.142 AC XY: 10535 AN XY: 74390

African (AFR) AF: 0.100 AC: 4158 AN: 41518

American (AMR) AF: 0.0985 AC: 1506 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5172

South Asian (SAS) AF: 0.112 AC: 542 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1966 AN: 10570

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

European-Non Finnish (NFE) AF: 0.174 AC: 11817 AN: 67992

Other (OTH) AF: 0.142 AC: 300 AN: 2108

Alfa AF: 0.159 Hom.: 5881

Bravo AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs6073629; hg19: chr20-43706559;