Variant 10-68827772-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_152709.5(STOX1):c.149A>C(p.Asn50Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000056 ( 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: 2.27

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STOX1	NM_152709.5 linkuse as main transcript	c.149A>C	p.Asn50Thr	missense_variant	1/4	ENST00000298596.11
STOX1	NM_001130161.4 linkuse as main transcript	c.149A>C	p.Asn50Thr	missense_variant	1/5
STOX1	NM_001130159.3 linkuse as main transcript	c.149A>C	p.Asn50Thr	missense_variant	1/4
STOX1	NM_001130160.3 linkuse as main transcript	c.149A>C	p.Asn50Thr	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11 linkuse as main transcript	c.149A>C	p.Asn50Thr	missense_variant	1/4	1	NM_152709.5	P4	Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

89234

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000430

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:

0.0000477

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000556

AC:

AN:

557626

Hom.:

Cov.:

AF XY:

0.0000382

AC XY:

AN XY:

262004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000976

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000270

Gnomad4 EAS exome

AF:

0.000586

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00127

Gnomad4 NFE exome

AF:

0.0000474

Gnomad4 OTH exome

AF:

0.0000533

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000336

AC:

AN:

89310

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

43504

show subpopulations

Gnomad4 AFR

AF:

0.0000429

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:

0.0000477

Gnomad4 OTH

AF:

0.00

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

Jan 22, 2024

The c.149A>C (p.N50T) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a A to C substitution at nucleotide position 149, causing the asparagine (N) at amino acid position 50 to be replaced by a threonine (T). 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

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.18

T;T;.;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.42

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.7

M;M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Uncertain

-2.5

D;D;.;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0060

D;D;.;D;D

Sift4G

Uncertain

0.0070

D;D;.;D;D

Polyphen

0.98

D;D;.;B;B

Vest4

0.44

MutPred

0.51

Gain of phosphorylation at N50 (P = 0.0789);Gain of phosphorylation at N50 (P = 0.0789);Gain of phosphorylation at N50 (P = 0.0789);Gain of phosphorylation at N50 (P = 0.0789);Gain of phosphorylation at N50 (P = 0.0789);

MVP

0.79

MPC

0.29

ClinPred

0.97

GERP RS

4.5

Varity_R

0.25

gMVP

0.34

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