Genetic Variant NM_152709.5:c.2474A>T (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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5 link	c.2474A>T	p.Asn825Ile	missense_variant	Exon 3 of 4	ENST00000298596.11	NP_689922.3	Q6ZVD7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11 link	c.2474A>T	p.Asn825Ile	missense_variant	Exon 3 of 4	1	NM_152709.5	ENSP00000298596.6		Q6ZVD7-1

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

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00439

AC:

ExAC

AF:

0.00354

AC:

428

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 v4.3

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

T;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.52

.;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.4

M;M;.

PhyloP100

-0.13

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.1

D;D;.

REVEL

Benign

0.21

Sift

Uncertain

0.016

D;D;.

Sift4G

Uncertain

0.051

T;T;.

Polyphen

0.85

P;P;.

Vest4

0.37

MVP

0.37

MPC

0.33

ClinPred

0.057

GERP RS

-4.2

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

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