rs1386133319

Variant names:

• chr10-68827757-C-G
• rs1386133319
• NM_152709.5:c.134C>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_152709.5(STOX1):​c.134C>G​(p.Ala45Gly) 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 0.000018 (0 hom., cov: 13)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.800

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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42173555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5	c.134C>G	p.Ala45Gly	missense_variant	Exon 1 of 4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.134C>G	p.Ala45Gly	missense_variant	Exon 1 of 4	1	NM_152709.5	ENSP00000298596.6

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 2 AN: 108404 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000702

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 Cov.: 8

GnomAD4 genome AF: 0.0000184 AC: 2 AN: 108474 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 52672

Gnomad4 AFR AF: 0.0000700

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134C>G (p.A45G) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a C to G substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.63	.;T;T;T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.95	L;L;.;L;L
PROVEAN	Benign	-1.2	N;N;.;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T;T;.;T;T
Sift4G	Benign	0.39	T;T;.;T;T
Polyphen		1.0	D;D;.;D;D
Vest4		0.24
MutPred		0.35		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.88
MPC		0.28
ClinPred		0.73	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.066

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: rs1386133319; hg19: chr10-70587514;