chr10-68827727-C-T

Variant names:

• chr10-68827727-C-T
• NM_152709.5:c.104C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152709.5(STOX1):​c.104C>T​(p.Ala35Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31495684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	NM_152709.5	MANE Select	c.104C>T	p.Ala35Val	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.104C>T	p.Ala35Val	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.104C>T	p.Ala35Val	missense	Exon 1 of 4	NP_001123631.1	Q6ZVD7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STOX1	ENST00000298596.11	TSL:1 MANE Select	c.104C>T	p.Ala35Val	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.104C>T	p.Ala35Val	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.104C>T	p.Ala35Val	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000140 AC: 1 AN: 712266 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 337602

African (AFR) AF: 0.00 AC: 0 AN: 13598

American (AMR) AF: 0.00 AC: 0 AN: 3672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6738

East Asian (EAS) AF: 0.00 AC: 0 AN: 10692

South Asian (SAS) AF: 0.00 AC: 0 AN: 13734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1634

European-Non Finnish (NFE) AF: 0.00000160 AC: 1 AN: 625164

Other (OTH) AF: 0.00 AC: 0 AN: 25924

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.27
Sift	Benign	0.26	T
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.26
MutPred		0.41		Loss of helix (P = 0.0033)
MVP		0.67
MPC		0.19
ClinPred		0.70	D
GERP RS		4.5
PromoterAI		-0.014	Neutral
Varity_R		0.10
gMVP		0.077
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr10-70587484;