rs6073627

Positions:

• chr20-45076910-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372806.8(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 ENST00000372806.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842

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=-0.84).
• 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	Protein	UniProt
STK4	NM_006282.5	c.*1734C>G		3_prime_UTR_variant	11/11	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.*1734C>G		3_prime_UTR_variant	11/11	1	NM_006282.5	ENSP00000361892	P1
STK4	ENST00000499879.7	c.*1734C>G		3_prime_UTR_variant	10/10	1		ENSP00000443514
STK4	ENST00000474717.3	c.*1734C>G		3_prime_UTR_variant	11/11	3		ENSP00000479564
STK4	ENST00000698228.1	n.5784C>G		non_coding_transcript_exon_variant	2/2

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

Gnomad4 FIN exome AF: 0.00

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

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.120

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs6073627; hg19: chr20-43705551;