13-98463584-TAAAAA-TAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001032296.4(STK24):c.929+106_929+107insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,030,050 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 0)
  • Exomes 𝑓: 0.014 (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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0143 (12676/887646) while in subpopulation AFR AF= 0.0486 (1021/21008). AF 95% confidence interval is 0.0461. There are 0 homozygotes in gnomad4_exome. There are 6308 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.929+106_929+107insT		intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.872+106_872+107insT		intron_variant
STK24	NM_003576.5	c.965+106_965+107insT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.929+106_929+107insT		intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 481 AN: 142372 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00501

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.000243

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00167

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.0143 AC: 12676 AN: 887646 Hom.: 0 AF XY: 0.0144 AC XY: 6308 AN XY: 437698

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.0178

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.00937

Gnomad4 SAS exome AF: 0.0264

Gnomad4 FIN exome AF: 0.00890

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.00337 AC: 480 AN: 142404 Hom.: 4 Cov.: 0 AF XY: 0.00377 AC XY: 260 AN XY: 68908

Gnomad4 AFR AF: 0.00505

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00501

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0175

Gnomad4 FIN AF: 0.000243

Gnomad4 NFE AF: 0.00167

Gnomad4 OTH AF: 0.00566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;