Genetic Variant STOX1:p.Leu582Phe (chr10-68885540-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152709.5(STOX1):c.1744C>T(p.Leu582Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,614,176 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 32)

Exomes 𝑓: 0.010 ( 103 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

Publications

12 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005161643).

BP6

Variant 10-68885540-C-T is Benign according to our data. Variant chr10-68885540-C-T is described in ClinVar as Benign. ClinVar VariationId is 2640537.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5 link	c.1744C>T	p.Leu582Phe	missense_variant	Exon 3 of 4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11 link	c.1744C>T	p.Leu582Phe	missense_variant	Exon 3 of 4	1	NM_152709.5	ENSP00000298596.6

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00766

AC:

1910

AN:

249376

AF XY:

0.00753

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00574

Gnomad ASJ exome

AF:

0.0256

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00417

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0105

AC:

15317

AN:

1461884

Hom.:

103

Cov.:

AF XY:

0.0102

AC XY:

7439

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

33478

American (AMR)

AF:

0.00635

AC:

284

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

662

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00293

AC:

253

AN:

86258

European-Finnish (FIN)

AF:

0.00519

AC:

277

AN:

53416

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0118

AC:

13175

AN:

1112008

Other (OTH)

AF:

0.00985

AC:

595

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

939

1878

2818

3757

4696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.00755

AC:

1150

AN:

152292

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41554

American (AMR)

AF:

0.0104

AC:

159

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00349

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

715

AN:

68018

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00935

Hom.:

Bravo

AF:

0.00816

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00262

AC:

ESP6500EA

AF:

0.0124

AC:

102

ExAC

AF:

0.00794

AC:

960

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 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

0.085

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;T;.

Eigen

Benign

0.010

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.0

.;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.0

M;M;.

PhyloP100

0.32

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

N;N;.

REVEL

Uncertain

0.31

Sift

Benign

0.093

T;T;.

Sift4G

Uncertain

0.034

D;D;.

Vest4

0.22

ClinPred

0.016

GERP RS

5.8

Varity_R

0.11

gMVP

0.018

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over