Genetic Variant STK24:c.440-20G>C (chr13-98474998-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001032296.4(STK24):c.440-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,597,190 control chromosomes in the GnomAD database, including 245,794 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 0.54 ( 22189 hom., cov: 32)

Exomes 𝑓: 0.55 ( 223605 hom. )

Consequence

STK24
NM_001032296.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.44

Publications

12 publications found

Variant links:

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

STK24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4 link	c.440-20G>C	intron_variant	Intron 4 of 10	ENST00000539966.6	NP_001027467.2	Q9Y6E0-2Q5U0E6Q6P0Y1
STK24	NM_003576.5 link	c.476-20G>C	intron_variant	Intron 4 of 10		NP_003567.2	Q9Y6E0-1
STK24	NM_001286649.2 link	c.383-20G>C	intron_variant	Intron 3 of 9		NP_001273578.1	B4DR80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6 link	c.440-20G>C		intron_variant	Intron 4 of 10	1	NM_001032296.4	ENSP00000442539.2		Q9Y6E0-2

Frequencies

GnomAD3 genomes

AF:

0.536

AC:

81414

AN:

152028

Hom.:

22167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.507

AC:

119079

AN:

235096

AF XY:

0.510

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.535

Gnomad EAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.512

GnomAD4 exome

AF:

0.552

AC:

797757

AN:

1445044

Hom.:

223605

Cov.:

AF XY:

0.550

AC XY:

395056

AN XY:

717910

show subpopulations

African (AFR)

AF:

0.545

AC:

17986

AN:

33020

American (AMR)

AF:

0.397

AC:

16919

AN:

42636

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

12972

AN:

24818

East Asian (EAS)

AF:

0.286

AC:

11311

AN:

39582

South Asian (SAS)

AF:

0.458

AC:

38332

AN:

83606

European-Finnish (FIN)

AF:

0.521

AC:

26883

AN:

51598

Middle Eastern (MID)

AF:

0.513

AC:

2907

AN:

5666

European-Non Finnish (NFE)

AF:

0.578

AC:

638421

AN:

1104368

Other (OTH)

AF:

0.536

AC:

32026

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

18060

36120

54181

72241

90301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17520

35040

52560

70080

87600

<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:

0.536

AC:

81482

AN:

152146

Hom.:

22189

Cov.:

AF XY:

0.526

AC XY:

39149

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.544

AC:

22572

AN:

41514

American (AMR)

AF:

0.456

AC:

6969

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

1838

AN:

3472

East Asian (EAS)

AF:

0.297

AC:

1536

AN:

5180

South Asian (SAS)

AF:

0.439

AC:

2111

AN:

4814

European-Finnish (FIN)

AF:

0.494

AC:

5235

AN:

10600

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39578

AN:

67966

Other (OTH)

AF:

0.522

AC:

1101

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1938

3876

5813

7751

9689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.511

Hom.:

2878

Bravo

AF:

0.528

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.015

(source)

DANN

Benign

0.42

PhyloP100

-5.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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