rs6017460

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-44995017-C-A
• chr20-44995017-C-G
• chr20-44995017-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

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

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000453 (415/917120) while in subpopulation EAS AF= 0.00176 (43/24444). AF 95% confidence interval is 0.00134. There are 0 homozygotes in gnomad4_exome. There are 236 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.526-73C>A		intron_variant	Intron 5 of 10	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.526-73C>A		intron_variant	Intron 5 of 10	1	NM_006282.5	ENSP00000361892.3

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

Gnomad4 AFR exome AF: 0.000733

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.000355

Gnomad4 FIN exome AF: 0.000850

Gnomad4 NFE exome AF: 0.000345

Gnomad4 OTH exome AF: 0.000649

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43623658;