rs9584854

chr13-98466336-C-T

Variant summary

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

The NM_001032296.4(STK24):c.783+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,589,048 control chromosomes in the GnomAD database, including 60,622 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 0.25 (4986 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55636 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

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 (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.783+40G>A		intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.726+40G>A		intron_variant
STK24	NM_003576.5	c.819+40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.783+40G>A		intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38398 AN: 152002 Hom.: 4978 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.251 AC: 59988 AN: 239066 Hom.: 7688 AF XY: 0.253 AC XY: 32699 AN XY: 129412

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.172

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.276 AC: 396165 AN: 1436928 Hom.: 55636 Cov.: 29 AF XY: 0.275 AC XY: 195902 AN XY: 712828

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.253 AC: 38430 AN: 152120 Hom.: 4986 Cov.: 33 AF XY: 0.249 AC XY: 18499 AN XY: 74368

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.248

Alfa AF: 0.276 Hom.: 7859

Bravo AF: 0.249

Asia WGS AF: 0.195 AC: 678 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	5.8
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9584854; hg19: chr13-99118590;