rs6073629

Positions:

• chr20-45077918-G-A
• chr20-45077918-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5	c.*2742G>A		3_prime_UTR_variant	11/11	ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8	c.*2742G>A		3_prime_UTR_variant	11/11	1	NM_006282.5	P1
STK4	ENST00000499879.7	c.*2742G>A		3_prime_UTR_variant	10/10	1
STK4	ENST00000474717.3	c.*2742G>A		3_prime_UTR_variant	11/11	3
STK4	ENST00000698228.1	n.6792G>A		non_coding_transcript_exon_variant	2/2

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.142

Alfa AF: 0.162 Hom.: 3422

Bravo AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs6073629; hg19: chr20-43706559;