dbSNP rs2289921: STK33:c.-159C>G (chr11-8475064-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001352389.2(STK33):c.-159C>G variant causes a 5 prime UTR premature start codon gain 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. 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 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

10 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
STK33	NM_001352389.2 link	c.-159C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 5 of 16	ENST00000687296.1	NP_001339318.1
STK33	NM_001352389.2 link	c.-159C>G	splice_region_variant	Exon 5 of 16	ENST00000687296.1	NP_001339318.1
STK33	NM_001352389.2 link	c.-159C>G	5_prime_UTR_variant	Exon 5 of 16	ENST00000687296.1	NP_001339318.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
STK33	ENST00000687296.1 link	c.-159C>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 5 of 16	NM_001352389.2	ENSP00000509322.1
STK33	ENST00000687296.1 link	c.-159C>G	splice_region_variant	Exon 5 of 16	NM_001352389.2	ENSP00000509322.1
STK33	ENST00000687296.1 link	c.-159C>G	5_prime_UTR_variant	Exon 5 of 16	NM_001352389.2	ENSP00000509322.1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68326

AN:

151888

Hom.:

15744

Cov.:

show subpopulations

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.:

AF XY:

0.477

AC XY:

90253

AN XY:

189406

show subpopulations

African (AFR)

AF:

0.338

AC:

3028

AN:

8966

American (AMR)

AF:

0.496

AC:

5034

AN:

10148

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

4280

AN:

11420

East Asian (EAS)

AF:

0.419

AC:

10664

AN:

25476

South Asian (SAS)

AF:

0.366

AC:

7667

AN:

20960

European-Finnish (FIN)

AF:

0.539

AC:

16222

AN:

30094

Middle Eastern (MID)

AF:

0.346

AC:

571

AN:

1650

European-Non Finnish (NFE)

AF:

0.501

AC:

117142

AN:

233948

Other (OTH)

AF:

0.467

AC:

10171

AN:

21784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4458

8916

13373

17831

22289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

922

1844

2766

3688

4610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.450

AC:

68370

AN:

152004

Hom.:

15758

Cov.:

AF XY:

0.450

AC XY:

33408

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.345

AC:

14314

AN:

41436

American (AMR)

AF:

0.473

AC:

7222

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1294

AN:

3468

East Asian (EAS)

AF:

0.440

AC:

2278

AN:

5172

South Asian (SAS)

AF:

0.355

AC:

1712

AN:

4820

European-Finnish (FIN)

AF:

0.540

AC:

5698

AN:

10552

Middle Eastern (MID)

AF:

0.390

AC:

114

AN:

292

European-Non Finnish (NFE)

AF:

0.504

AC:

34236

AN:

67968

Other (OTH)

AF:

0.432

AC:

910

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1890

3780

5669

7559

9449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.82

PhyloP100

2.7

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=295/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over