rs2274055

Positions:

• chr13-98475242-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.439+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,596,924 control chromosomes in the GnomAD database, including 65,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6545 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59317 hom.)
• Consequence: STK24 NM_001032296.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006093
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.439+8G>A		splice_region_variant, intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.382+8G>A		splice_region_variant, intron_variant
STK24	NM_003576.5	c.475+8G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.439+8G>A		splice_region_variant, intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43963 AN: 151978 Hom.: 6540 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.280

GnomAD3 exomes AF: 0.257 AC: 62874 AN: 244930 Hom.: 8566 AF XY: 0.257 AC XY: 34051 AN XY: 132254

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.283 AC: 409294 AN: 1444828 Hom.: 59317 Cov.: 28 AF XY: 0.282 AC XY: 202619 AN XY: 719412

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.289 AC: 43996 AN: 152096 Hom.: 6545 Cov.: 32 AF XY: 0.283 AC XY: 21077 AN XY: 74360

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.282

Alfa AF: 0.293 Hom.: 4905

Bravo AF: 0.286

Asia WGS AF: 0.197 AC: 684 AN: 3478

EpiCase AF: 0.292

EpiControl AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.82
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0
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: rs2274055; hg19: chr13-99127496; COSMIC: COSV64823706;