Genetic Variant STOX1:p.Arg18Pro (chr10-68827676-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PS1_ModerateBP4_StrongBP6_ModerateBS2

The NM_152709.5(STOX1):c.53G>C(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,121,884 control chromosomes in the GnomAD database, including 31 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 Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0062 ( 30 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.22

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 -8 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=0.008164227).

BP6

Variant 10-68827676-G-C is Benign according to our data. Variant chr10-68827676-G-C is described in ClinVar as [Benign]. Clinvar id is 3341721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 1 of 4	ENST00000298596.11	NP_689922.3	Q6ZVD7-1
STOX1	NM_001130161.4 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 1 of 5		NP_001123633.1	Q6ZVD7-1
STOX1	NM_001130159.3 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 1 of 4		NP_001123631.1	Q6ZVD7-2
STOX1	NM_001130160.3 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 1 of 3		NP_001123632.1	Q6ZVD7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11 link	c.53G>C	p.Arg18Pro	missense_variant	Exon 1 of 4	1	NM_152709.5	ENSP00000298596.6		Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

572

AN:

147280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00735

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.0102

AC:

AN:

884

Hom.:

AF XY:

0.0133

AC XY:

AN XY:

600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00619

AC:

6029

AN:

974500

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

2853

AN XY:

458920

show subpopulations

Gnomad4 AFR exome

AF:

0.000367

Gnomad4 AMR exome

AF:

0.000748

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000531

Gnomad4 FIN exome

AF:

0.00457

Gnomad4 NFE exome

AF:

0.00682

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00388

AC:

572

AN:

147384

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

247

AN XY:

71786

show subpopulations

Gnomad4 AFR

AF:

0.00117

Gnomad4 AMR

AF:

0.000268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00337

Gnomad4 NFE

AF:

0.00735

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.00336

Hom.:

Bravo

AF:

0.00335

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STOX1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

T;T;.;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.52

.;T;T;T;T

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.0082

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.41

N;N;.;N;N

PROVEAN

Benign

-1.5

N;N;.;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.20

T;T;.;T;T

Sift4G

Benign

0.20

T;T;.;T;T

Polyphen

0.056

B;B;.;B;B

Vest4

0.35

MPC

0.10

ClinPred

0.050

GERP RS

3.1

Varity_R

0.32

gMVP

0.49

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