Genetic Variant STK24:c.929+106dupT (chr13-98463584-T-TA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001032296.4(STK24):c.929+106dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,030,050 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 0)

Exomes 𝑓: 0.014 ( 0 hom. )

Consequence

STK24
NM_001032296.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 4 gene

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
STK24	NM_001032296.4	MANE Select	c.929+106dupT	intron	N/A	NP_001027467.2
STK24	NM_003576.5		c.965+106dupT	intron	N/A	NP_003567.2
STK24	NM_001286649.2		c.872+106dupT	intron	N/A	NP_001273578.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK24	ENST00000539966.6	TSL:1 MANE Select	c.929+106_929+107insT	intron	N/A	ENSP00000442539.2
STK24	ENST00000376547.7	TSL:1	c.965+106_965+107insT	intron	N/A	ENSP00000365730.3
STK24	ENST00000444574.1	TSL:1	c.680+106_680+107insT	intron	N/A	ENSP00000402764.1

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

481

AN:

142372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00501

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.000243

Gnomad MID

AF:

0.00667

Gnomad NFE

AF:

0.00167

Gnomad OTH

AF:

0.00623

GnomAD4 exome

AF:

0.0143

AC:

12676

AN:

887646

Hom.:

AF XY:

0.0144

AC XY:

6308

AN XY:

437698

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0486

AC:

1021

AN:

21008

American (AMR)

AF:

0.0178

AC:

272

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0158

AC:

229

AN:

14514

East Asian (EAS)

AF:

0.00937

AC:

260

AN:

27758

South Asian (SAS)

AF:

0.0264

AC:

1233

AN:

46758

European-Finnish (FIN)

AF:

0.00890

AC:

224

AN:

25174

Middle Eastern (MID)

AF:

0.0189

AC:

AN:

4028

European-Non Finnish (NFE)

AF:

0.0126

AC:

8765

AN:

694482

Other (OTH)

AF:

0.0154

AC:

596

AN:

38610

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.284

Heterozygous variant carriers

1177

2354

3532

4709

5886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

364

728

1092

1456

1820

<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:

0.00337

AC:

480

AN:

142404

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

260

AN XY:

68908

show subpopulations

African (AFR)

AF:

0.00505

AC:

195

AN:

38642

American (AMR)

AF:

0.00464

AC:

AN:

14428

Ashkenazi Jewish (ASJ)

AF:

0.00501

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4892

South Asian (SAS)

AF:

0.0175

AC:

AN:

4452

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

8226

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00167

AC:

109

AN:

65256

Other (OTH)

AF:

0.00566

AC:

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over