Genetic Variant STK24:p.Pro356Pro (chr13-98460426-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001032296.4(STK24):c.1068G>A(p.Pro356Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,613,452 control chromosomes in the GnomAD database, including 806,353 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 1.0 ( 75961 hom., cov: 31)

Exomes 𝑓: 1.0 ( 730392 hom. )

Consequence

STK24
NM_001032296.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.708

Publications

14 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.177).

BP7

Synonymous conserved (PhyloP=0.708 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
STK24	NM_001032296.4 link	c.1068G>A	p.Pro356Pro	synonymous_variant	Exon 9 of 11	ENST00000539966.6	NP_001027467.2
STK24	NM_003576.5 link	c.1104G>A	p.Pro368Pro	synonymous_variant	Exon 9 of 11		NP_003567.2
STK24	NM_001286649.2 link	c.1011G>A	p.Pro337Pro	synonymous_variant	Exon 8 of 10		NP_001273578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6 link	c.1068G>A	p.Pro356Pro	synonymous_variant	Exon 9 of 11	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

151999

AN:

152198

Hom.:

75900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.996

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD2 exomes

AF:

1.00

AC:

250810

AN:

250910

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.995

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1460960

AN:

1461136

Hom.:

730392

Cov.:

AF XY:

1.00

AC XY:

726784

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.996

AC:

33351

AN:

33470

American (AMR)

AF:

0.999

AC:

44673

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26122

AN:

26122

East Asian (EAS)

AF:

1.00

AC:

39696

AN:

39696

South Asian (SAS)

AF:

1.00

AC:

86199

AN:

86200

European-Finnish (FIN)

AF:

1.00

AC:

53340

AN:

53340

Middle Eastern (MID)

AF:

1.00

AC:

5764

AN:

5764

European-Non Finnish (NFE)

AF:

1.00

AC:

1111457

AN:

1111462

Other (OTH)

AF:

1.00

AC:

60358

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.999

AC:

152119

AN:

152316

Hom.:

75961

Cov.:

AF XY:

0.999

AC XY:

74375

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.996

AC:

41371

AN:

41552

American (AMR)

AF:

0.999

AC:

15293

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5182

AN:

5182

South Asian (SAS)

AF:

1.00

AC:

4826

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68033

AN:

68034

Other (OTH)

AF:

0.999

AC:

2114

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.999

Hom.:

47728

Bravo

AF:

0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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