10-68886270-A-T

Position:

• chr10-68886270-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PS1_Moderate BP4_Strong BS2

The NM_152709.5(STOX1):​c.2474A>T​(p.Asn825Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,613,998 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (10 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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 Likely_benign. Variant got -6 ACMG points.

• PS1: Transcript NM_152709.5 (STOX1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• BP4: Computational evidence support a benign effect (MetaRNN=0.0067908466).
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5	c.2474A>T	p.Asn825Ile	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.2474A>T	p.Asn825Ile	missense_variant	3/4	1	NM_152709.5	ENSP00000298596	P4

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 356 AN: 151992 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000894

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00267 AC: 667 AN: 249568 Hom.: 4 AF XY: 0.00275 AC XY: 372 AN XY: 135398

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000752

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00517

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00362 AC: 5298 AN: 1461888 Hom.: 10 Cov.: 34 AF XY: 0.00358 AC XY: 2600 AN XY: 727248

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000696

Gnomad4 FIN exome AF: 0.00133

Gnomad4 NFE exome AF: 0.00449

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00233 AC: 355 AN: 152110 Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74340

Gnomad4 AFR AF: 0.000891

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00422

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00347 Hom.: 3

Bravo AF: 0.00214

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00439 AC: 36

ExAC AF: 0.00354 AC: 428

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00294

EpiControl AF: 0.00403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.52	.;T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.0068	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.4	M;M;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.016	D;D;.
Sift4G	Uncertain	0.051	T;T;.
Polyphen		0.85	P;P;.
Vest4		0.37
MVP		0.37
MPC		0.33
ClinPred		0.057	T
GERP RS		-4.2
Varity_R		0.19
gMVP		0.057

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: rs41278532; hg19: chr10-70646026;