13-98460500-T-G

Variant summary

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

The NM_001032296.4(STK24):c.1054-60A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,445,150 control chromosomes in the GnomAD database, including 512,569 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 0.74 (43900 hom., cov: 32)
  • Exomes 𝑓: 0.85 (468669 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.1054-60A>C		intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.997-60A>C		intron_variant
STK24	NM_003576.5	c.1090-60A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.1054-60A>C		intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112484 AN: 151844 Hom.: 43890 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.846 AC: 1093699 AN: 1293188 Hom.: 468669 AF XY: 0.842 AC XY: 548272 AN XY: 650790

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.883

Gnomad4 NFE exome AF: 0.887

Gnomad4 OTH exome AF: 0.823

GnomAD4 genome AF: 0.741 AC: 112529 AN: 151962 Hom.: 43900 Cov.: 32 AF XY: 0.739 AC XY: 54881 AN XY: 74274

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.761

Alfa AF: 0.829 Hom.: 11067

Bravo AF: 0.715

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.95
Dann	Benign	0.46

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: rs4772083; hg19: chr13-99112754; COSMIC: COSV64823384;