NM_152709.5:c.226C>A

Variant names:

• chr10-68827849-C-A
• rs1218169616
• NM_152709.5:c.226C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152709.5(STOX1):​c.226C>A​(p.Pro76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P76S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 8)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.240
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2645963).

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.226C>A	p.Pro76Thr	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.226C>A	p.Pro76Thr	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.226C>A	p.Pro76Thr	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.226C>A	p.Pro76Thr	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.226C>A	p.Pro76Thr	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.226C>A	p.Pro76Thr	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes AF: 0.000275 AC: 16 AN: 58078 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00208

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 AF: 0.0000237 AC: 4 AN: 168850 Hom.: 0 Cov.: 4 AF XY: 0.0000246 AC XY: 2 AN XY: 81180

African (AFR) AF: 0.00 AC: 0 AN: 3178

American (AMR) AF: 0.00 AC: 0 AN: 598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1164

East Asian (EAS) AF: 0.00 AC: 0 AN: 1194

South Asian (SAS) AF: 0.00 AC: 0 AN: 3228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000263 AC: 4 AN: 151864

Other (OTH) AF: 0.00 AC: 0 AN: 5932

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000275 AC: 16 AN: 58078 Hom.: 0 Cov.: 8 AF XY: 0.000419 AC XY: 12 AN XY: 28644

African (AFR) AF: 0.00 AC: 0 AN: 14346

American (AMR) AF: 0.00208 AC: 16 AN: 7708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1496

East Asian (EAS) AF: 0.00 AC: 0 AN: 1576

South Asian (SAS) AF: 0.00 AC: 0 AN: 1456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3670

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26862

Other (OTH) AF: 0.00 AC: 0 AN: 680

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	0.17
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.24
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Benign	0.21	T
Sift4G	Benign	0.18	T
Polyphen		0.96	D
Vest4		0.26
MutPred		0.38		Gain of MoRF binding (P = 0.0801)
MVP		0.64
MPC		0.27
ClinPred		0.58	D
GERP RS		3.1
PromoterAI		-0.015	Neutral
Varity_R		0.070
gMVP		0.10
Mutation Taster		=83/17	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: rs1218169616; hg19: chr10-70587606;