rs4868146

Positions:

• chr5-172154441-G-A
• chr5-172154441-G-C

Variant summary

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

The NM_005990.4(STK10):​c.321+2183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,014 control chromosomes in the GnomAD database, including 13,921 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 0.41 (13921 hom., cov: 32)
• Consequence: STK10 NM_005990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

Genes affected

STK10 (HGNC:11388): (serine/threonine kinase 10) This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. [provided by RefSeq, Jul 2008]

STK10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK10	NM_005990.4	c.321+2183C>T		intron_variant		ENST00000176763.10	NP_005981.3
STK10	XM_047417628.1	c.321+2183C>T		intron_variant			XP_047273584.1
STK10	XM_047417629.1	c.321+2183C>T		intron_variant			XP_047273585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK10	ENST00000176763.10	c.321+2183C>T		intron_variant		1	NM_005990.4	ENSP00000176763.5
STK10	ENST00000519710.1	n.102+2183C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61924 AN: 151896 Hom.: 13900 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61998 AN: 152014 Hom.: 13921 Cov.: 32 AF XY: 0.400 AC XY: 29713 AN XY: 74310

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.402

Alfa AF: 0.353 Hom.: 19699

Bravo AF: 0.424

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.63

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: rs4868146; hg19: chr5-171581445; COSMIC: COSV51571992;