Variant 10-68884359-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_152709.5(STOX1):c.563C>A(p.Thr188Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,098 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.83

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014918834).

BP6

Variant 10-68884359-C-A is Benign according to our data. Variant chr10-68884359-C-A is described in ClinVar as [Benign]. Clinvar id is 717159.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1707/152318) while in subpopulation AFR AF= 0.0383 (1592/41568). AF 95% confidence interval is 0.0367. There are 35 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOX1	NM_152709.5 linkuse as main transcript	c.563C>A	p.Thr188Asn	missense_variant	3/4	ENST00000298596.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11 linkuse as main transcript	c.563C>A	p.Thr188Asn	missense_variant	3/4	1	NM_152709.5	P4	Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1704

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00303

AC:

755

AN:

249126

Hom.:

AF XY:

0.00229

AC XY:

310

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000239

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00128

AC:

1865

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

808

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0425

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.0112

AC:

1707

AN:

152318

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0383

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0369

AC:

139

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00363

AC:

439

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.060

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.65

D;D;.;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.0

M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.5

D;D;.;D

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;.;D

Polyphen

1.0

D;D;.;D

Vest4

0.89

MVP

0.86

MPC

0.44

ClinPred

0.026

GERP RS

5.6

Varity_R

0.85

gMVP

0.87

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