Genetic Variant STOX1:p.Asn825Ile (chr10-68886270-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152709.5(STOX1):c.2474A>T(p.Asn825Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,613,998 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 10 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.130

Publications

8 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

new If you want to explore the variant's impact on the transcript NM_152709.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067908466).

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

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.2474A>T	p.Asn825Ile	missense	Exon 3 of 4	NP_689922.3
STOX1	NM_001130161.4		c.2474A>T	p.Asn825Ile	missense	Exon 3 of 5	NP_001123633.1	Q6ZVD7-1
STOX1	NM_001130159.3		c.663+1811A>T		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.2474A>T	p.Asn825Ile	missense	Exon 3 of 4	ENSP00000298596.6	Q6ZVD7-1
STOX1	ENST00000399169.8	TSL:1	c.2474A>T	p.Asn825Ile	missense	Exon 3 of 5	ENSP00000382121.4	Q6ZVD7-1
STOX1	ENST00000399165.8	TSL:1	c.663+1811A>T		intron	N/A	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00422

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00267

AC:

667

AN:

249568

AF XY:

0.00275

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.00517

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00362

AC:

5298

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

2600

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.000514

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00133

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00449

AC:

4991

AN:

1112006

Other (OTH)

AF:

0.00220

AC:

133

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

357

714

1071

1428

1785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.00233

AC:

355

AN:

152110

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000891

AC:

AN:

41510

American (AMR)

AF:

0.000524

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00422

AC:

287

AN:

67968

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

104

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:

0.00347

Hom.:

Bravo

AF:

0.00214

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.52

M_CAP

Benign

0.069

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.4

PhyloP100

-0.13

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.21

Sift

Uncertain

0.016

Sift4G

Uncertain

0.051

Varity_R

0.19

gMVP

0.057

Mutation Taster

=100/0

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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STOX1 p.Asn825Ile

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