chr13-98474798-C-T

Variant names:

• chr13-98474798-C-T
• rs9582232
• NM_001032296.4:c.597+23G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032296.4(STK24):​c.597+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,593,352 control chromosomes in the GnomAD database, including 27,962 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 0.16 (2019 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25943 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.597+23G>A		intron_variant	Intron 5 of 10	ENST00000539966.6	NP_001027467.2
STK24	NM_003576.5	c.633+23G>A		intron_variant	Intron 5 of 10		NP_003567.2
STK24	NM_001286649.2	c.540+23G>A		intron_variant	Intron 4 of 9		NP_001273578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.597+23G>A		intron_variant	Intron 5 of 10	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23823 AN: 152086 Hom.: 2015 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.167 AC: 39040 AN: 234254 AF XY: 0.170

Gnomad AFR exome AF: 0.0950

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.187 AC: 269628 AN: 1441148 Hom.: 25943 Cov.: 31 AF XY: 0.187 AC XY: 133501 AN XY: 715462

African (AFR) AF: 0.0932 AC: 3061 AN: 32848

American (AMR) AF: 0.124 AC: 5198 AN: 41868

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5312 AN: 24562

East Asian (EAS) AF: 0.114 AC: 4502 AN: 39364

South Asian (SAS) AF: 0.160 AC: 13247 AN: 82980

European-Finnish (FIN) AF: 0.165 AC: 8704 AN: 52660

Middle Eastern (MID) AF: 0.218 AC: 1142 AN: 5250

European-Non Finnish (NFE) AF: 0.197 AC: 217490 AN: 1102216

Other (OTH) AF: 0.185 AC: 10972 AN: 59400

GnomAD4 genome AF: 0.157 AC: 23835 AN: 152204 Hom.: 2019 Cov.: 32 AF XY: 0.154 AC XY: 11477 AN XY: 74406

African (AFR) AF: 0.0949 AC: 3941 AN: 41540

American (AMR) AF: 0.137 AC: 2102 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3470

East Asian (EAS) AF: 0.131 AC: 680 AN: 5176

South Asian (SAS) AF: 0.157 AC: 755 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1699 AN: 10602

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13316 AN: 67986

Other (OTH) AF: 0.177 AC: 374 AN: 2112

Alfa AF: 0.181 Hom.: 530

Bravo AF: 0.154

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.83
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9582232; hg19: chr13-99127052; COSMIC: COSV64823703; COSMIC: COSV64823703;