11-8482627-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK33	NM_001352389.2	c.-465-2013G>C		intron_variant		ENST00000687296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK33	ENST00000687296.1	c.-465-2013G>C		intron_variant			NM_001352389.2	P1

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

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.443

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.62

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: rs12806736; hg19: chr11-8504174;