13-98463673-A-G

Position:

• chr13-98463673-A-G

Variant summary

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

The NM_001032296.4(STK24):​c.929+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,610,040 control chromosomes in the GnomAD database, including 590,033 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 0.83 (52222 hom., cov: 31)
  • Exomes 𝑓: 0.86 (537811 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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 = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK24	NM_001032296.4	c.929+18T>C		intron_variant		ENST00000539966.6	NP_001027467.2
STK24	NM_003576.5	c.965+18T>C		intron_variant			NP_003567.2
STK24	NM_001286649.2	c.872+18T>C		intron_variant			NP_001273578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.929+18T>C		intron_variant		1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125333 AN: 151876 Hom.: 52181 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.812

GnomAD3 exomes AF: 0.793 AC: 197259 AN: 248680 Hom.: 80083 AF XY: 0.796 AC XY: 106998 AN XY: 134484

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.773

Gnomad EAS exome AF: 0.720

Gnomad SAS exome AF: 0.663

Gnomad FIN exome AF: 0.889

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.855 AC: 1247024 AN: 1458046 Hom.: 537811 Cov.: 46 AF XY: 0.850 AC XY: 616438 AN XY: 724980

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.838

GnomAD4 genome AF: 0.825 AC: 125421 AN: 151994 Hom.: 52222 Cov.: 31 AF XY: 0.821 AC XY: 60946 AN XY: 74278

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.812

Alfa AF: 0.849 Hom.: 9838

Bravo AF: 0.809

Asia WGS AF: 0.728 AC: 2531 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	0.92
DANN	Benign	0.15

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: rs2296149; hg19: chr13-99115927; COSMIC: COSV64823070;