chr10-68885540-C-T

Variant names:

• chr10-68885540-C-T
• rs41278530
• NM_152709.5:c.1744C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152709.5(STOX1):​c.1744C>T​(p.Leu582Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,614,176 control chromosomes in the GnomAD database, including 111 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (8 hom., cov: 32)
  • Exomes 𝑓: 0.010 (103 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.315
• Publications: 12 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005161643).
• BP6: Variant 10-68885540-C-T is Benign according to our data. Variant chr10-68885540-C-T is described in ClinVar as Benign. ClinVar VariationId is 2640537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	NM_152709.5	MANE Select	c.1744C>T	p.Leu582Phe	missense	Exon 3 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.1744C>T	p.Leu582Phe	missense	Exon 3 of 5	NP_001123633.1
	STOX1	NM_001130159.3		c.663+1081C>T		intron	N/A	NP_001123631.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	ENST00000298596.11	TSL:1 MANE Select	c.1744C>T	p.Leu582Phe	missense	Exon 3 of 4	ENSP00000298596.6
	STOX1	ENST00000399169.8	TSL:1	c.1744C>T	p.Leu582Phe	missense	Exon 3 of 5	ENSP00000382121.4
	STOX1	ENST00000399165.8	TSL:1	c.663+1081C>T		intron	N/A	ENSP00000382118.4

Frequencies

GnomAD3 genomes AF: 0.00756 AC: 1150 AN: 152174 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00766 AC: 1910 AN: 249376 AF XY: 0.00753

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00417

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0105 AC: 15317 AN: 1461884 Hom.: 103 Cov.: 33 AF XY: 0.0102 AC XY: 7439 AN XY: 727244

African (AFR) AF: 0.00137 AC: 46 AN: 33478

American (AMR) AF: 0.00635 AC: 284 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 662 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00293 AC: 253 AN: 86258

European-Finnish (FIN) AF: 0.00519 AC: 277 AN: 53416

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.0118 AC: 13175 AN: 1112008

Other (OTH) AF: 0.00985 AC: 595 AN: 60396

GnomAD4 genome AF: 0.00755 AC: 1150 AN: 152292 Hom.: 8 Cov.: 32 AF XY: 0.00708 AC XY: 527 AN XY: 74462

African (AFR) AF: 0.00209 AC: 87 AN: 41554

American (AMR) AF: 0.0104 AC: 159 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 715 AN: 68018

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00935 Hom.: 24

Bravo AF: 0.00816

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00262 AC: 10

ESP6500EA AF: 0.0124 AC: 102

ExAC AF: 0.00794 AC: 960

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STOX1: BP4, BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.010
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.32
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.31
Sift	Benign	0.093	T
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.22
MVP		0.42
MPC		0.33
ClinPred		0.016	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.018
Mutation Taster		=100/0	polymorphism

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: rs41278530; hg19: chr10-70645296;