13-98463584-TAAAAA-TAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001032296.4(STK24):c.929+105_929+106del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,037,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0374 (33474/895394) while in subpopulation AMR AF= 0.0475 (734/15462). AF 95% confidence interval is 0.0446. There are 0 homozygotes in gnomad4_exome. There are 16417 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.929+105_929+106del		intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.872+105_872+106del		intron_variant
STK24	NM_003576.5	c.965+105_965+106del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.929+105_929+106del		intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.000738 AC: 105 AN: 142372 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.000815

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00279

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000644

Gnomad OTH AF: 0.00104

GnomAD4 exome AF: 0.0374 AC: 33474 AN: 895394 Hom.: 0 AF XY: 0.0372 AC XY: 16417 AN XY: 441628

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.0348

Gnomad4 EAS exome AF: 0.0367

Gnomad4 SAS exome AF: 0.0422

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0360

GnomAD4 genome AF: 0.000737 AC: 105 AN: 142404 Hom.: 0 Cov.: 0 AF XY: 0.000755 AC XY: 52 AN XY: 68910

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.000818

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00279

Gnomad4 NFE AF: 0.000644

Gnomad4 OTH AF: 0.00103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56325686; hg19: chr13-99115838;