Variant 10-68827735-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152709.5(STOX1):c.112C>T(p.Arg38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 134,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 28)

Consequence

STOX1
NM_152709.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0690

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STOX1	NM_152709.5 linkuse as main transcript	c.112C>T	p.Arg38Cys	missense_variant	1/4	ENST00000298596.11
STOX1	NM_001130161.4 linkuse as main transcript	c.112C>T	p.Arg38Cys	missense_variant	1/5
STOX1	NM_001130159.3 linkuse as main transcript	c.112C>T	p.Arg38Cys	missense_variant	1/4
STOX1	NM_001130160.3 linkuse as main transcript	c.112C>T	p.Arg38Cys	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11 linkuse as main transcript	c.112C>T	p.Arg38Cys	missense_variant	1/4	1	NM_152709.5	P4	Q6ZVD7-1

Frequencies

GnomAD3 genomes

AF:

0.00000743

AC:

AN:

134520

Hom.:

Cov.:

show subpopulations

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:

0.000243

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000743

AC:

AN:

134520

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

65048

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:

0.000243

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

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

Jun 03, 2022

The c.112C>T (p.R38C) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a C to T substitution at nucleotide position 112, causing the arginine (R) at amino acid position 38 to be replaced by a cysteine (C). 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

Benign

0.29

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;.;.;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.45

M_CAP

Pathogenic

1.0

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.6

L;L;.;L;L

MutationTaster

Benign

0.91

D;D;D;D

PROVEAN

Benign

-2.3

N;N;.;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.011

D;D;.;D;D

Sift4G

Uncertain

0.017

D;D;.;D;D

Polyphen

1.0

D;D;.;D;D

Vest4

0.32

MutPred

0.41

Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);

MVP

0.59

MPC

0.48

ClinPred

0.68

GERP RS

3.5

Varity_R

0.14

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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