rs7904300

Positions:

• chr10-68886383-G-A

Variant summary

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

The NM_152709.5(STOX1):​c.2587G>A​(p.Ala863Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,614,168 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.028 (201 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (164 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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=0.0018880069).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5	c.2587G>A	p.Ala863Thr	missense_variant	3/4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.2587G>A	p.Ala863Thr	missense_variant	3/4	1	NM_152709.5	ENSP00000298596.6

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4291 AN: 152166 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0181

GnomAD3 exomes AF: 0.00709 AC: 1769 AN: 249356 Hom.: 77 AF XY: 0.00523 AC XY: 707 AN XY: 135268

Gnomad AFR exome AF: 0.0976

Gnomad AMR exome AF: 0.00553

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00330

GnomAD4 exome AF: 0.00291 AC: 4261 AN: 1461882 Hom.: 164 Cov.: 34 AF XY: 0.00241 AC XY: 1752 AN XY: 727240

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.0282 AC: 4301 AN: 152286 Hom.: 201 Cov.: 32 AF XY: 0.0262 AC XY: 1952 AN XY: 74470

Gnomad4 AFR AF: 0.0978

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00631 Hom.: 73

Bravo AF: 0.0331

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0949 AC: 385

ESP6500EA AF: 0.000474 AC: 4

ExAC AF: 0.00848 AC: 1026

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.0
DANN	Benign	0.85
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.54	.;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.72	N;N;.
REVEL	Benign	0.10
Sift	Benign	0.29	T;T;.
Sift4G	Benign	0.12	T;T;.
Polyphen		0.036	B;B;.
Vest4		0.057
MVP		0.14
MPC		0.076
ClinPred		0.0011	T
GERP RS		-1.5
Varity_R		0.040
gMVP		0.043

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: rs7904300; hg19: chr10-70646139;