10-68882104-T-G

Position:

• chr10-68882104-T-G

Variant summary

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

The NM_152709.5(STOX1):​c.457T>G​(p.Tyr153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y153H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STOX1	NM_152709.5	c.457T>G	p.Tyr153Asp	missense_variant	2/4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.457T>G	p.Tyr153Asp	missense_variant	2/4	1	NM_152709.5	ENSP00000298596.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D;D;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	.;T;T;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.4	M;M;.;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.3	D;D;.;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.015	D;D;.;D;T
Sift4G	Uncertain	0.0070	D;D;.;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.76
MutPred		0.64		Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);.;Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);
MVP		0.79
MPC		0.54
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.60
gMVP		0.73

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: rs1341667; hg19: chr10-70641860;