rs2289921

chr11-8475064-G-Cchr11-8475064-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001352389.2(STK33):c.-159C>G variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 516,450 control chromosomes in the GnomAD database, including 58,544 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15758 hom., cov: 32)
  • Exomes 𝑓: 0.48 (42786 hom.)
• Consequence: STK33 NM_001352389.2 splice_region, 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK33	NM_001352389.2	c.-159C>G		splice_region_variant, 5_prime_UTR_variant	5/16	ENST00000687296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK33	ENST00000687296.1	c.-159C>G		splice_region_variant, 5_prime_UTR_variant	5/16		NM_001352389.2	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68326 AN: 151888 Hom.: 15744 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.480 AC: 174779 AN: 364446 Hom.: 42786 Cov.: 5 AF XY: 0.477 AC XY: 90253 AN XY: 189406

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.450 AC: 68370 AN: 152004 Hom.: 15758 Cov.: 32 AF XY: 0.450 AC XY: 33408 AN XY: 74310

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.432

Alfa AF: 0.461 Hom.: 1983

Bravo AF: 0.446

Asia WGS AF: 0.390 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	13
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2289921; hg19: chr11-8496611;