Variant rs41278532 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PS1_ModerateBP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PS1

Transcript NM_152709.5 (STOX1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

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/exons	MANE	Protein	UniProt
STOX1	NM_152709.5 linkuse as main transcript	c.2474A>T	p.Asn825Ile	missense_variant	3/4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11 linkuse as main transcript	c.2474A>T	p.Asn825Ile	missense_variant	3/4	1	NM_152709.5	ENSP00000298596	P4	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

GnomAD3 exomes

AF:

0.00267

AC:

667

AN:

249568

Hom.:

AF XY:

0.00275

AC XY:

372

AN XY:

135398

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 SAS exome

AF:

0.000752

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

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00449

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00233

AC:

355

AN:

152110

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00422

Gnomad4 OTH

AF:

0.00189

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

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;.

MutationTaster

Benign

1.0

N;N;N;N;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over