dbSNP rs1041585341: STOX1:p.Gly26Arg (chr10-68827699-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152709.5(STOX1):c.76G>A(p.Gly26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000958 in 949,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.508

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09440458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOX1	NM_152709.5	MANE Select	c.76G>A	p.Gly26Arg	missense	Exon 1 of 4	NP_689922.3
STOX1	NM_001130161.4		c.76G>A	p.Gly26Arg	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
STOX1	NM_001130159.3		c.76G>A	p.Gly26Arg	missense	Exon 1 of 4	NP_001123631.1	Q6ZVD7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STOX1	ENST00000298596.11	TSL:1 MANE Select	c.76G>A	p.Gly26Arg	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
STOX1	ENST00000399169.8	TSL:1	c.76G>A	p.Gly26Arg	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
STOX1	ENST00000399165.8	TSL:1	c.76G>A	p.Gly26Arg	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes

AF:

0.0000824

AC:

AN:

145636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000168

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000971

AC:

AN:

803698

Hom.:

Cov.:

AF XY:

0.0000973

AC XY:

AN XY:

380448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15632

American (AMR)

AF:

0.00

AC:

AN:

4702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8416

East Asian (EAS)

AF:

0.00

AC:

AN:

14566

South Asian (SAS)

AF:

0.00

AC:

AN:

15462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1960

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

698338

Other (OTH)

AF:

0.0000333

AC:

AN:

30018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000892

AC:

AN:

145740

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

70938

show subpopulations

African (AFR)

AF:

0.0000247

AC:

AN:

40514

American (AMR)

AF:

0.00

AC:

AN:

14798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

4828

South Asian (SAS)

AF:

0.00

AC:

AN:

4720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000168

AC:

AN:

65458

Other (OTH)

AF:

0.000496

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

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:

0.000108

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.011

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

PhyloP100

0.51

PROVEAN

Benign

-1.3

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.010

Vest4

0.040

MutPred

0.24

Gain of MoRF binding (P = 0.0152)

MVP

0.21

MPC

0.087

ClinPred

0.076

GERP RS

0.77

PromoterAI

0.031

Neutral

(source)

Varity_R

0.045

gMVP

0.13

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over