10-68827808-T-C

Variant names:

• chr10-68827808-T-C
• NM_152709.5:c.185T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152709.5(STOX1):​c.185T>C​(p.Phe62Ser) 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: 10)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• 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 0 ACMG points.

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.185T>C	p.Phe62Ser	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.185T>C	p.Phe62Ser	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.185T>C	p.Phe62Ser	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.185T>C	p.Phe62Ser	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.185T>C	p.Phe62Ser	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.185T>C	p.Phe62Ser	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000269 AC: 1 AN: 371790 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 176332

African (AFR) AF: 0.00 AC: 0 AN: 6870

American (AMR) AF: 0.00 AC: 0 AN: 988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2612

East Asian (EAS) AF: 0.00 AC: 0 AN: 2482

South Asian (SAS) AF: 0.000139 AC: 1 AN: 7184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 336028

Other (OTH) AF: 0.00 AC: 0 AN: 12658

GnomAD4 genome Cov.: 10

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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.4
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.63		Gain of loop (P = 0.0051)
MVP		0.78
MPC		0.53
ClinPred		0.99	D
GERP RS		4.4
PromoterAI		0.0051	Neutral
Varity_R		0.61
gMVP		0.41
Mutation Taster		=75/25	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: chr10-70587565;