10-68882104-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152709.5(STOX1):c.457T>C(p.Tyr153His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,612,536 control chromosomes in the GnomAD database, including 329,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (26523 hom., cov: 31)
  • Exomes 𝑓: 0.64 (302583 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.99

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8438457E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOX1	NM_152709.5	c.457T>C	p.Tyr153His	missense_variant	2/4	ENST00000298596.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11	c.457T>C	p.Tyr153His	missense_variant	2/4	1	NM_152709.5	P4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87808 AN: 151850 Hom.: 26520 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.581

GnomAD3 exomes AF: 0.624 AC: 155696 AN: 249428 Hom.: 50017 AF XY: 0.627 AC XY: 84892 AN XY: 135336

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.597

Gnomad EAS exome AF: 0.908

Gnomad SAS exome AF: 0.599

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.640 AC: 935250 AN: 1460568 Hom.: 302583 Cov.: 38 AF XY: 0.639 AC XY: 464478 AN XY: 726640

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.680

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.578 AC: 87841 AN: 151968 Hom.: 26523 Cov.: 31 AF XY: 0.584 AC XY: 43367 AN XY: 74276

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.585

Alfa AF: 0.630 Hom.: 65232

Bravo AF: 0.561

TwinsUK AF: 0.652 AC: 2418

ALSPAC AF: 0.655 AC: 2523

ESP6500AA AF: 0.416 AC: 1532

ESP6500EA AF: 0.642 AC: 5240

ExAC AF: 0.623 AC: 75251

Asia WGS AF: 0.691 AC: 2402 AN: 3478

EpiCase AF: 0.633

EpiControl AF: 0.630

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Preeclampsia/eclampsia 4 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 04, 2012

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;.;.;.
Eigen	Benign	-0.043
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.0000018	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	N;N;.;N;N
MutationTaster	Benign	0.076	P;P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.3	D;D;.;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.33	T;T;.;T;T
Sift4G	Benign	0.21	T;T;.;T;D
Polyphen		0.47	P;P;.;B;P
Vest4		0.14
MPC		0.23
ClinPred		0.019	T
GERP RS		4.4
Varity_R		0.29
gMVP		0.65

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

Other links and lift over

dbSNP: rs1341667; hg19: chr10-70641860; COSMIC: COSV53816198;