13-98463673-A-G

Variant names:

• chr13-98463673-A-G
• rs2296149
• NM_001032296.4:c.929+18T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032296.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	NM_001032296.4	MANE Select	c.929+18T>C		intron	N/A	NP_001027467.2
	STK24	NM_003576.5		c.965+18T>C		intron	N/A	NP_003567.2
	STK24	NM_001286649.2		c.872+18T>C		intron	N/A	NP_001273578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.929+18T>C		intron	N/A	ENSP00000442539.2
	STK24	ENST00000376547.7	TSL:1	c.965+18T>C		intron	N/A	ENSP00000365730.3
	STK24	ENST00000444574.1	TSL:1	c.680+18T>C		intron	N/A	ENSP00000402764.1

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

GnomAD2 exomes AF: 0.793 AC: 197259 AN: 248680 AF XY: 0.796

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 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

African (AFR) AF: 0.781 AC: 26067 AN: 33358

American (AMR) AF: 0.605 AC: 26798 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 20148 AN: 25962

East Asian (EAS) AF: 0.743 AC: 29440 AN: 39618

South Asian (SAS) AF: 0.669 AC: 57443 AN: 85926

European-Finnish (FIN) AF: 0.884 AC: 47058 AN: 53212

Middle Eastern (MID) AF: 0.748 AC: 4308 AN: 5760

European-Non Finnish (NFE) AF: 0.888 AC: 985245 AN: 1109646

Other (OTH) AF: 0.838 AC: 50517 AN: 60250

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

African (AFR) AF: 0.789 AC: 32657 AN: 41406

American (AMR) AF: 0.706 AC: 10792 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2692 AN: 3472

East Asian (EAS) AF: 0.723 AC: 3733 AN: 5162

South Asian (SAS) AF: 0.660 AC: 3184 AN: 4824

European-Finnish (FIN) AF: 0.884 AC: 9306 AN: 10530

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60234 AN: 68002

Other (OTH) AF: 0.812 AC: 1710 AN: 2106

Alfa AF: 0.850 Hom.: 17825

Bravo AF: 0.809

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.92
DANN	Benign	0.15
PhyloP100		0.012
PromoterAI		0.0027	Neutral
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: rs2296149; hg19: chr13-99115927; COSMIC: COSV64823070;