Variant 10-68827868-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_152709.5(STOX1):c.245T>C(p.Val82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000081 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.384

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2734418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STOX1	NM_152709.5 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	1/4	ENST00000298596.11
STOX1	NM_001130161.4 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	1/5
STOX1	NM_001130159.3 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	1/4
STOX1	NM_001130160.3 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	1/4	1	NM_152709.5	P4	Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

42490

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000813

AC:

AN:

110656

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

53482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000905

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000706

AC:

AN:

42490

Hom.:

Cov.:

AF XY:

0.0000476

AC XY:

AN XY:

20996

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.245T>C (p.V82A) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a T to C substitution at nucleotide position 245, causing the valine (V) at amino acid position 82 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

Cadd

Benign

Dann

Benign

0.53

DEOGEN2

Benign

0.028

T;T;.;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.29

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.8

L;L;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PROVEAN

Benign

-1.7

N;N;.;N;D

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;.;D;T

Sift4G

Benign

0.14

T;T;.;T;T

Polyphen

0.37

B;B;.;B;B

Vest4

0.53

MutPred

0.37

Gain of disorder (P = 0.0384);Gain of disorder (P = 0.0384);Gain of disorder (P = 0.0384);Gain of disorder (P = 0.0384);Gain of disorder (P = 0.0384);

MVP

0.62

MPC

0.39

ClinPred

0.68

GERP RS

3.1

Varity_R

0.29

gMVP

0.16

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