chr10-68827832-T-C

Position:

• chr10-68827832-T-C

Variant summary

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

The ENST00000298596.11(STOX1):​c.209T>C​(p.Val70Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 9)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: STOX1 ENST00000298596.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.452

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5	c.209T>C	p.Val70Ala	missense_variant	1/4	ENST00000298596.11	NP_689922.3
STOX1	NM_001130161.4	c.209T>C	p.Val70Ala	missense_variant	1/5		NP_001123633.1
STOX1	NM_001130159.3	c.209T>C	p.Val70Ala	missense_variant	1/4		NP_001123631.1
STOX1	NM_001130160.3	c.209T>C	p.Val70Ala	missense_variant	1/3		NP_001123632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.209T>C	p.Val70Ala	missense_variant	1/4	1	NM_152709.5	ENSP00000298596	P4

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome AF: 0.00000423 AC: 1 AN: 236300 Hom.: 0 Cov.: 5 AF XY: 0.00000886 AC XY: 1 AN XY: 112868

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000470

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 9

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

Jun 19, 2024

The c.209T>C (p.V70A) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a T to C substitution at nucleotide position 209, causing the valine (V) at amino acid position 70 to be replaced by an alanine (A). 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	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T;T;.;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.47	.;T;T;T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.6	M;M;.;M;M
MutationTaster	Benign	0.71	D;D;D;D;D
PROVEAN	Benign	-1.8	N;N;.;N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.026	D;D;.;D;D
Sift4G	Uncertain	0.023	D;D;.;D;D
Polyphen		0.80	P;P;.;B;B
Vest4		0.38
MutPred		0.37		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.57
MPC		0.45
ClinPred		0.62	D
GERP RS		2.6
Varity_R		0.048
gMVP		0.17

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: chr10-70587589;