Genetic Variant NM_001032296.4: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032296.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK24	NM_001032296.4	MANE Select	c.440-20G>C	intron	N/A	NP_001027467.2	Q9Y6E0-2
STK24	NM_003576.5		c.476-20G>C	intron	N/A	NP_003567.2
STK24	NM_001286649.2		c.383-20G>C	intron	N/A	NP_001273578.1	B4DR80

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK24	ENST00000539966.6	TSL:1 MANE Select	c.440-20G>C	intron	N/A	ENSP00000442539.2	Q9Y6E0-2
STK24	ENST00000376547.7	TSL:1	c.476-20G>C	intron	N/A	ENSP00000365730.3	Q9Y6E0-1
STK24	ENST00000444574.1	TSL:1	c.191-20G>C	intron	N/A	ENSP00000402764.1	H0Y630

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over