rs1341667

Variant names:

• chr10-68882104-T-C
• rs1341667
• NM_152709.5:c.457T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-68882104-T-C
• chr10-68882104-T-A
• chr10-68882104-T-G

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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
• Publications: 77 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	NM_152709.5	MANE Select	c.457T>C	p.Tyr153His	missense	Exon 2 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.457T>C	p.Tyr153His	missense	Exon 2 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.457T>C	p.Tyr153His	missense	Exon 2 of 4	NP_001123631.1	Q6ZVD7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	ENST00000298596.11	TSL:1 MANE Select	c.457T>C	p.Tyr153His	missense	Exon 2 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.457T>C	p.Tyr153His	missense	Exon 2 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.457T>C	p.Tyr153His	missense	Exon 2 of 4	ENSP00000382118.4	Q6ZVD7-2

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

GnomAD2 exomes AF: 0.624 AC: 155696 AN: 249428 AF XY: 0.627

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 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

African (AFR) AF: 0.394 AC: 13190 AN: 33456

American (AMR) AF: 0.530 AC: 23696 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 15627 AN: 26116

East Asian (EAS) AF: 0.842 AC: 33362 AN: 39604

South Asian (SAS) AF: 0.602 AC: 51943 AN: 86226

European-Finnish (FIN) AF: 0.680 AC: 36312 AN: 53392

Middle Eastern (MID) AF: 0.599 AC: 3447 AN: 5758

European-Non Finnish (NFE) AF: 0.647 AC: 719283 AN: 1110964

Other (OTH) AF: 0.636 AC: 38390 AN: 60332

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

African (AFR) AF: 0.406 AC: 16823 AN: 41416

American (AMR) AF: 0.565 AC: 8631 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2114 AN: 3468

East Asian (EAS) AF: 0.889 AC: 4604 AN: 5176

South Asian (SAS) AF: 0.606 AC: 2919 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7191 AN: 10544

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.642 AC: 43652 AN: 67970

Other (OTH) AF: 0.585 AC: 1231 AN: 2106

Alfa AF: 0.617 Hom.: 91804

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

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Preeclampsia/eclampsia 4 (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.043
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	N
PhyloP100		3.0
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.35
Sift	Benign	0.33	T
Sift4G	Benign	0.21	T
Polyphen		0.47	P
Vest4		0.14
MPC		0.23
ClinPred		0.019	T
GERP RS		4.4
Varity_R		0.29
gMVP		0.65
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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