rs10769908

Variant names:

• chr11-8462542-C-T
• rs10769908
• NM_001352389.2:c.454-633G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352389.2(STK33):​c.454-633G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 150,746 control chromosomes in the GnomAD database, including 23,229 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 0.55 (23229 hom., cov: 27)
• Consequence: STK33 NM_001352389.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 33 publications found

Genes affected

STK33 (HGNC:14568): (serine/threonine kinase 33) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in mitotic DNA damage checkpoint signaling and protein autophosphorylation. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STK33 Gene-Disease associations (from GenCC):

• spermatogenic failure 93

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352389.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK33	NM_001352389.2	MANE Select	c.454-633G>A		intron	N/A	NP_001339318.1	Q9BYT3-1
	STK33	NM_001289061.2		c.454-633G>A		intron	N/A	NP_001275990.1	Q9BYT3-1
	STK33	NM_001352387.2		c.454-633G>A		intron	N/A	NP_001339316.1	Q9BYT3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK33	ENST00000687296.1	MANE Select	c.454-633G>A		intron	N/A	ENSP00000509322.1	Q9BYT3-1
	STK33	ENST00000315204.5	TSL:1	c.454-633G>A		intron	N/A	ENSP00000320754.1	Q9BYT3-1
	STK33	ENST00000447869.5	TSL:1	c.454-633G>A		intron	N/A	ENSP00000416750.1	Q9BYT3-1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 82920 AN: 150632 Hom.: 23203 Cov.: 27

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.551 AC: 82989 AN: 150746 Hom.: 23229 Cov.: 27 AF XY: 0.551 AC XY: 40495 AN XY: 73494

African (AFR) AF: 0.654 AC: 26785 AN: 40952

American (AMR) AF: 0.528 AC: 7966 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2871 AN: 5104

South Asian (SAS) AF: 0.646 AC: 3067 AN: 4748

European-Finnish (FIN) AF: 0.463 AC: 4768 AN: 10304

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33668 AN: 67776

Other (OTH) AF: 0.571 AC: 1196 AN: 2096

Alfa AF: 0.525 Hom.: 38290

Bravo AF: 0.554

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10769908; hg19: chr11-8484089;