11-8482627-C-G

Variant names:

• chr11-8482627-C-G
• rs12806736
• NM_001352389.2:c.-465-2013G>C

Variant summary

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

The NM_001352389.2(STK33):​c.-465-2013G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,948 control chromosomes in the GnomAD database, including 12,057 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 0.39 (12057 hom., cov: 32)
• Consequence: STK33 NM_001352389.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.547 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.-465-2013G>C		intron	N/A	NP_001339318.1	Q9BYT3-1
	STK33	NM_001289061.2		c.-161-7561G>C		intron	N/A	NP_001275990.1	Q9BYT3-1
	STK33	NM_001352387.2		c.-195-5344G>C		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.-465-2013G>C		intron	N/A	ENSP00000509322.1	Q9BYT3-1
	STK33	ENST00000315204.5	TSL:1	c.-161-7561G>C		intron	N/A	ENSP00000320754.1	Q9BYT3-1
	STK33	ENST00000526517.1	TSL:1	n.178-29721G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59758 AN: 151830 Hom.: 12054 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.394 AC: 59802 AN: 151948 Hom.: 12057 Cov.: 32 AF XY: 0.397 AC XY: 29514 AN XY: 74270

African (AFR) AF: 0.336 AC: 13935 AN: 41430

American (AMR) AF: 0.418 AC: 6384 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2572 AN: 5174

South Asian (SAS) AF: 0.565 AC: 2718 AN: 4812

European-Finnish (FIN) AF: 0.348 AC: 3661 AN: 10526

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27440 AN: 67952

Other (OTH) AF: 0.443 AC: 933 AN: 2108

Alfa AF: 0.262 Hom.: 626

Bravo AF: 0.389

Asia WGS AF: 0.543 AC: 1888 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	1.2
DANN	Benign	0.62
PhyloP100		-0.29
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: rs12806736; hg19: chr11-8504174;