Genetic Variant STOX1:p.Arg18Gln (chr10-68827676-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152709.5(STOX1):c.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 974,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31576413).

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.53G>A	p.Arg18Gln	missense	Exon 1 of 4	NP_689922.3
STOX1	NM_001130161.4		c.53G>A	p.Arg18Gln	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
STOX1	NM_001130159.3		c.53G>A	p.Arg18Gln	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.53G>A	p.Arg18Gln	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
STOX1	ENST00000399169.8	TSL:1	c.53G>A	p.Arg18Gln	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
STOX1	ENST00000399165.8	TSL:1	c.53G>A	p.Arg18Gln	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

974520

Hom.:

Cov.:

AF XY:

0.00000654

AC XY:

AN XY:

458930

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19074

American (AMR)

AF:

0.00

AC:

AN:

5348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9932

East Asian (EAS)

AF:

0.0000600

AC:

AN:

16670

South Asian (SAS)

AF:

0.00

AC:

AN:

18822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2364

European-Non Finnish (NFE)

AF:

0.00000470

AC:

AN:

850224

Other (OTH)

AF:

0.0000277

AC:

AN:

36126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.3

PhyloP100

2.2

PROVEAN

Benign

-1.3

REVEL

Benign

0.27

Sift

Benign

0.096

Sift4G

Benign

0.073

Polyphen

0.98

Vest4

0.18

MutPred

0.37

Loss of MoRF binding (P = 0.0658)

MVP

0.80

MPC

0.16

ClinPred

0.83

GERP RS

3.1

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.049

gMVP

0.26

Mutation Taster

=94/6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over