10-68884398-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152709.5(STOX1):c.602A>G(p.Glu201Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106315106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STOX1	NM_152709.5	c.602A>G	p.Glu201Gly	missense_variant	3/4	ENST00000298596.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STOX1	ENST00000298596.11	c.602A>G	p.Glu201Gly	missense_variant	3/4	1	NM_152709.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.602A>G (p.E201G) alteration is located in exon 3 (coding exon 3) of the STOX1 gene. This alteration results from a A to G substitution at nucleotide position 602, causing the glutamic acid (E) at amino acid position 201 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	0.072
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.4	L;L;.;L
MutationTaster	Benign	0.51	D;D;D;D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N;N;.;N
REVEL	Benign	0.080
Sift	Benign	0.15	T;T;.;T
Sift4G	Benign	0.47	T;T;.;T
Polyphen		0.022	B;B;.;B
Vest4		0.058
MutPred		0.27		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;Gain of loop (P = 0.0312);
MVP		0.50
MPC		0.082
ClinPred		0.40	T
GERP RS		3.2
Varity_R		0.071
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-70644154;