Variant 10-68882104-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152709.5(STOX1):c.457T>C(p.Tyr153His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,612,536 control chromosomes in the GnomAD database, including 329,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.58 ( 26523 hom., cov: 31)

Exomes 𝑓: 0.64 ( 302583 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 2.99

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8438457E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5 link	c.457T>C	p.Tyr153His	missense_variant	2/4	ENST00000298596.11	NP_689922.3	Q6ZVD7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11 link	c.457T>C	p.Tyr153His	missense_variant	2/4	1	NM_152709.5	ENSP00000298596.6		Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87808

AN:

151850

Hom.:

26520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.581

GnomAD3 exomes

AF:

0.624

AC:

155696

AN:

249428

Hom.:

50017

AF XY:

0.627

AC XY:

84892

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.597

Gnomad EAS exome

AF:

0.908

Gnomad SAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.638

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.640

AC:

935250

AN:

1460568

Hom.:

302583

Cov.:

AF XY:

0.639

AC XY:

464478

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.394

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.598

Gnomad4 EAS exome

AF:

0.842

Gnomad4 SAS exome

AF:

0.602

Gnomad4 FIN exome

AF:

0.680

Gnomad4 NFE exome

AF:

0.647

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.578

AC:

87841

AN:

151968

Hom.:

26523

Cov.:

AF XY:

0.584

AC XY:

43367

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.406

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.610

Gnomad4 EAS

AF:

0.889

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.682

Gnomad4 NFE

AF:

0.642

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.630

Hom.:

65232

Bravo

AF:

0.561

TwinsUK

AF:

0.652

AC:

2418

ALSPAC

AF:

0.655

AC:

2523

ESP6500AA

AF:

0.416

AC:

1532

ESP6500EA

AF:

0.642

AC:

5240

ExAC

AF:

0.623

AC:

75251

Asia WGS

AF:

0.691

AC:

2402

AN:

3478

EpiCase

AF:

0.633

EpiControl

AF:

0.630

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Preeclampsia/eclampsia 4

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 04, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;.;.;.

Eigen

Benign

-0.043

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.68

.;T;T;T;T

MetaRNN

Benign

0.0000018

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.60

N;N;.;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

D;D;.;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.33

T;T;.;T;T

Sift4G

Benign

0.21

T;T;.;T;D

Polyphen

0.47

P;P;.;B;P

Vest4

0.14

MPC

0.23

ClinPred

0.019

GERP RS

4.4

Varity_R

0.29

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over