NM_152709.5:c.1824A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152709.5(STOX1):c.1824A>C(p.Glu608Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,614,008 control chromosomes in the GnomAD database, including 37,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E608E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.18 ( 2875 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34580 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -1.56

Publications

39 publications found

Variant links:

Genes affected

STOX1 (HGNC:23508): (storkhead box 1) Enables RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including positive regulation of G2/M transition of mitotic cell cycle; positive regulation of protein phosphorylation; and regulation of gene expression. Located in centrosome; cytosol; and nuclear lumen. Implicated in pre-eclampsia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

STOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005174637).

BP6

Variant 10-68885620-A-C is Benign according to our data. Variant chr10-68885620-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOX1	NM_152709.5	MANE Select	c.1824A>C	p.Glu608Asp	missense	Exon 3 of 4	NP_689922.3
STOX1	NM_001130161.4		c.1824A>C	p.Glu608Asp	missense	Exon 3 of 5	NP_001123633.1	Q6ZVD7-1
STOX1	NM_001130159.3		c.663+1161A>C		intron	N/A	NP_001123631.1	Q6ZVD7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOX1	ENST00000298596.11	TSL:1 MANE Select	c.1824A>C	p.Glu608Asp	missense	Exon 3 of 4	ENSP00000298596.6	Q6ZVD7-1
STOX1	ENST00000399169.8	TSL:1	c.1824A>C	p.Glu608Asp	missense	Exon 3 of 5	ENSP00000382121.4	Q6ZVD7-1
STOX1	ENST00000399165.8	TSL:1	c.663+1161A>C		intron	N/A	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26816

AN:

152074

Hom.:

2866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0991

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.178

GnomAD2 exomes

AF:

0.219

AC:

54508

AN:

249390

AF XY:

0.220

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.0816

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.213

AC:

312084

AN:

1461816

Hom.:

34580

Cov.:

AF XY:

0.215

AC XY:

156424

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0535

AC:

1790

AN:

33480

American (AMR)

AF:

0.300

AC:

13407

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6341

AN:

26136

East Asian (EAS)

AF:

0.153

AC:

6064

AN:

39700

South Asian (SAS)

AF:

0.230

AC:

19878

AN:

86258

European-Finnish (FIN)

AF:

0.258

AC:

13750

AN:

53398

Middle Eastern (MID)

AF:

0.195

AC:

1122

AN:

5768

European-Non Finnish (NFE)

AF:

0.214

AC:

237701

AN:

1111956

Other (OTH)

AF:

0.199

AC:

12031

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15498

30995

46493

61990

77488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8120

16240

24360

32480

40600

<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:

0.176

AC:

26835

AN:

152192

Hom.:

2875

Cov.:

AF XY:

0.180

AC XY:

13393

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0591

AC:

2455

AN:

41556

American (AMR)

AF:

0.232

AC:

3540

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

823

AN:

3470

East Asian (EAS)

AF:

0.0993

AC:

514

AN:

5176

South Asian (SAS)

AF:

0.233

AC:

1126

AN:

4824

European-Finnish (FIN)

AF:

0.266

AC:

2813

AN:

10580

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14842

AN:

67990

Other (OTH)

AF:

0.177

AC:

373

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1110

2221

3331

4442

5552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.203

Hom.:

11361

Bravo

AF:

0.169

TwinsUK

AF:

0.208

AC:

772

ALSPAC

AF:

0.211

AC:

812

ESP6500AA

AF:

0.0583

AC:

225

ESP6500EA

AF:

0.215

AC:

1779

ExAC

AF:

0.212

AC:

25628

Asia WGS

AF:

0.202

AC:

700

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.218

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Preeclampsia/eclampsia 4 (2)

Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0070

(source)

DANN

Benign

0.090

DEOGEN2

Benign

0.0072

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.6

PhyloP100

-1.6

PrimateAI

Benign

0.23

PROVEAN

Benign

0.96

REVEL

Benign

0.16

Sift

Benign

0.98

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.016

MutPred

0.35

Loss of sheet (P = 0.0817)

MPC

0.064

ClinPred

0.0042

GERP RS

1.1

Varity_R

0.041

gMVP

0.024

Mutation Taster

=99/1

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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