10-68827853-C-T

Variant names:

• chr10-68827853-C-T
• rs1411340638
• NM_152709.5:c.230C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152709.5(STOX1):​c.230C>T​(p.Pro77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P77R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0000064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0670
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25024903).

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.230C>T	p.Pro77Leu	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.230C>T	p.Pro77Leu	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.230C>T	p.Pro77Leu	missense	Exon 1 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.230C>T	p.Pro77Leu	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.230C>T	p.Pro77Leu	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.230C>T	p.Pro77Leu	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes AF: 0.000162 AC: 9 AN: 55660 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.000656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000641 AC: 1 AN: 155904 Hom.: 0 Cov.: 4 AF XY: 0.0000134 AC XY: 1 AN XY: 74890

African (AFR) AF: 0.000341 AC: 1 AN: 2936

American (AMR) AF: 0.00 AC: 0 AN: 570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1066

East Asian (EAS) AF: 0.00 AC: 0 AN: 1094

South Asian (SAS) AF: 0.00 AC: 0 AN: 3012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 140158

Other (OTH) AF: 0.00 AC: 0 AN: 5470

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000162 AC: 9 AN: 55660 Hom.: 0 Cov.: 7 AF XY: 0.000182 AC XY: 5 AN XY: 27502

African (AFR) AF: 0.000656 AC: 9 AN: 13720

American (AMR) AF: 0.00 AC: 0 AN: 7416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1460

East Asian (EAS) AF: 0.00 AC: 0 AN: 1492

South Asian (SAS) AF: 0.00 AC: 0 AN: 1418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 25756

Other (OTH) AF: 0.00 AC: 0 AN: 636

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.067
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.17
Sift	Benign	0.032	D
Sift4G	Benign	0.062	T
Polyphen		0.022	B
Vest4		0.20
MutPred		0.38		Loss of catalytic residue at P76 (P = 0.0131)
MVP		0.62
MPC		0.30
ClinPred		0.91	D
GERP RS		1.9
PromoterAI		-0.036	Neutral
Varity_R		0.068
gMVP		0.15
Mutation Taster		=293/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1411340638; hg19: chr10-70587610;