rs10840070

Variant names:

• chr11-8546660-C-T
• rs10840070
• NM_001352389.2:c.-466+47423G>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.-466+47423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 146,926 control chromosomes in the GnomAD database, including 11,707 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 0.40 (11707 hom., cov: 27)
• Consequence: STK33 NM_001352389.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK33	NM_001352389.2	c.-466+47423G>A		intron_variant	Intron 1 of 15	ENST00000687296.1	NP_001339318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK33	ENST00000687296.1	c.-466+47423G>A		intron_variant	Intron 1 of 15		NM_001352389.2	ENSP00000509322.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 59292 AN: 146820 Hom.: 11704 Cov.: 27

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.404 AC: 59315 AN: 146926 Hom.: 11707 Cov.: 27 AF XY: 0.405 AC XY: 28892 AN XY: 71284

African (AFR) AF: 0.433 AC: 17308 AN: 40000

American (AMR) AF: 0.385 AC: 5602 AN: 14542

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1319 AN: 3442

East Asian (EAS) AF: 0.330 AC: 1553 AN: 4700

South Asian (SAS) AF: 0.497 AC: 2263 AN: 4550

European-Finnish (FIN) AF: 0.406 AC: 3896 AN: 9594

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26152 AN: 66860

Other (OTH) AF: 0.399 AC: 818 AN: 2050

Alfa AF: 0.387 Hom.: 19588

Bravo AF: 0.390

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.22
PhyloP100		-0.92
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: rs10840070; hg19: chr11-8568207;