chr13-98460426-C-T

Position:

• chr13-98460426-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001032296.4(STK24):​c.1068G>A​(p.Pro356Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,613,452 control chromosomes in the GnomAD database, including 806,353 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 1.0 (75961 hom., cov: 31)
  • Exomes 𝑓: 1.0 (730392 hom.)
• Consequence: STK24 NM_001032296.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.708 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK24	NM_001032296.4	c.1068G>A	p.Pro356Pro	synonymous_variant	9/11	ENST00000539966.6	NP_001027467.2
STK24	NM_003576.5	c.1104G>A	p.Pro368Pro	synonymous_variant	9/11		NP_003567.2
STK24	NM_001286649.2	c.1011G>A	p.Pro337Pro	synonymous_variant	8/10		NP_001273578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.1068G>A	p.Pro356Pro	synonymous_variant	9/11	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.999 AC: 151999 AN: 152198 Hom.: 75900 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD3 exomes AF: 1.00 AC: 250810 AN: 250910 Hom.: 125356 AF XY: 1.00 AC XY: 135647 AN XY: 135684

Gnomad AFR exome AF: 0.995

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1460960 AN: 1461136 Hom.: 730392 Cov.: 41 AF XY: 1.00 AC XY: 726784 AN XY: 726860

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.999 AC: 152119 AN: 152316 Hom.: 75961 Cov.: 31 AF XY: 0.999 AC XY: 74375 AN XY: 74472

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.999

Alfa AF: 1.00 Hom.: 41949

Bravo AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4771305; hg19: chr13-99112680;