chr10-68827786-C-G

Position:

• chr10-68827786-C-G

Variant summary

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

The NM_152709.5(STOX1):​c.163C>G​(p.Arg55Gly) 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: not found (cov: 10)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

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=0.3898964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5	c.163C>G	p.Arg55Gly	missense_variant	1/4	ENST00000298596.11	NP_689922.3
STOX1	NM_001130161.4	c.163C>G	p.Arg55Gly	missense_variant	1/5		NP_001123633.1
STOX1	NM_001130159.3	c.163C>G	p.Arg55Gly	missense_variant	1/4		NP_001123631.1
STOX1	NM_001130160.3	c.163C>G	p.Arg55Gly	missense_variant	1/3		NP_001123632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.163C>G	p.Arg55Gly	missense_variant	1/4	1	NM_152709.5	ENSP00000298596	P4

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 10

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

Mar 31, 2024

The c.163C>G (p.R55G) 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 163, causing the arginine (R) at amino acid position 55 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	0.15
BayesDel_addAF	Benign	-0.00046	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T;.;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.59	.;T;T;T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.0	M;M;.;M;M
MutationTaster	Benign	0.80	N;N;N;N
PROVEAN	Benign	-2.1	N;N;.;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D;D;.;T;T
Sift4G	Uncertain	0.0090	D;D;.;T;T
Polyphen		0.14	B;B;.;B;B
Vest4		0.38
MutPred		0.38		Loss of methylation at R55 (P = 0.0464);Loss of methylation at R55 (P = 0.0464);Loss of methylation at R55 (P = 0.0464);Loss of methylation at R55 (P = 0.0464);Loss of methylation at R55 (P = 0.0464);
MVP		0.48
MPC		0.42
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.24
gMVP		0.14

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: chr10-70587543;