rs1407078032

Variant names:

• chr10-68827868-T-C
• rs1407078032
• NM_152709.5:c.245T>C

Variant summary

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

The NM_152709.5(STOX1):​c.245T>C​(p.Val82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000081 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.384
• 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=0.2734418).

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.245T>C	p.Val82Ala	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.245T>C	p.Val82Ala	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.245T>C	p.Val82Ala	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.245T>C	p.Val82Ala	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.245T>C	p.Val82Ala	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.245T>C	p.Val82Ala	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes AF: 0.0000706 AC: 3 AN: 42490 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

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: 0.000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000813 AC: 9 AN: 110656 Hom.: 0 Cov.: 4 AF XY: 0.0000374 AC XY: 2 AN XY: 53482

African (AFR) AF: 0.00 AC: 0 AN: 2022

American (AMR) AF: 0.00 AC: 0 AN: 384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 830

East Asian (EAS) AF: 0.00 AC: 0 AN: 748

South Asian (SAS) AF: 0.00 AC: 0 AN: 2110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000905 AC: 9 AN: 99466

Other (OTH) AF: 0.00 AC: 0 AN: 3866

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000706 AC: 3 AN: 42490 Hom.: 0 Cov.: 6 AF XY: 0.0000476 AC XY: 1 AN XY: 20996

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10060

American (AMR) AF: 0.00 AC: 0 AN: 5942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1182

East Asian (EAS) AF: 0.00 AC: 0 AN: 1162

South Asian (SAS) AF: 0.00 AC: 0 AN: 1060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 126

European-Non Finnish (NFE) AF: 0.000151 AC: 3 AN: 19916

Other (OTH) AF: 0.00 AC: 0 AN: 474

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Benign	0.53
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.38
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Polyphen		0.37	B
Vest4		0.53
MutPred		0.37		Gain of disorder (P = 0.0384)
MVP		0.62
MPC		0.39
ClinPred		0.68	D
GERP RS		3.1
PromoterAI		0.25	Neutral
Varity_R		0.29
gMVP		0.16
Mutation Taster		=70/30	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: rs1407078032; hg19: chr10-70587625;