chr13-98474998-C-G

Variant names:

• chr13-98474998-C-G
• rs9513430
• NM_001032296.4:c.440-20G>C

Variant summary

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

The NM_001032296.4(STK24):​c.440-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,597,190 control chromosomes in the GnomAD database, including 245,794 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 0.54 (22189 hom., cov: 32)
  • Exomes 𝑓: 0.55 (223605 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.44

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.440-20G>C		intron_variant	Intron 4 of 10	ENST00000539966.6	NP_001027467.2
STK24	NM_003576.5	c.476-20G>C		intron_variant	Intron 4 of 10		NP_003567.2
STK24	NM_001286649.2	c.383-20G>C		intron_variant	Intron 3 of 9		NP_001273578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.440-20G>C		intron_variant	Intron 4 of 10	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81414 AN: 152028 Hom.: 22167 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.507 AC: 119079 AN: 235096 Hom.: 31000 AF XY: 0.510 AC XY: 64720 AN XY: 126942

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.311

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.552 AC: 797757 AN: 1445044 Hom.: 223605 Cov.: 52 AF XY: 0.550 AC XY: 395056 AN XY: 717910

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.536 AC: 81482 AN: 152146 Hom.: 22189 Cov.: 32 AF XY: 0.526 AC XY: 39149 AN XY: 74394

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.522

Alfa AF: 0.511 Hom.: 2878

Bravo AF: 0.528

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.015
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9513430; hg19: chr13-99127252; COSMIC: COSV64823329;