rs556362193

Variant names:

• chr10-68827676-G-A
• rs556362193
• NM_152709.5:c.53G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-68827676-G-A
• chr10-68827676-G-C
• chr10-68827676-G-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.53G>A​(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 974,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 3 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=0.31576413).

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.53G>A	p.Arg18Gln	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.53G>A	p.Arg18Gln	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.53G>A	p.Arg18Gln	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.53G>A	p.Arg18Gln	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.53G>A	p.Arg18Gln	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.53G>A	p.Arg18Gln	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000616 AC: 6 AN: 974520 Hom.: 0 Cov.: 24 AF XY: 0.00000654 AC XY: 3 AN XY: 458930

African (AFR) AF: 0.00 AC: 0 AN: 19074

American (AMR) AF: 0.00 AC: 0 AN: 5348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9932

East Asian (EAS) AF: 0.0000600 AC: 1 AN: 16670

South Asian (SAS) AF: 0.00 AC: 0 AN: 18822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2364

European-Non Finnish (NFE) AF: 0.00000470 AC: 4 AN: 850224

Other (OTH) AF: 0.0000277 AC: 1 AN: 36126

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.2
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Benign	0.096	T
Sift4G	Benign	0.073	T
Polyphen		0.98	D
Vest4		0.18
MutPred		0.37		Loss of MoRF binding (P = 0.0658)
MVP		0.80
MPC		0.16
ClinPred		0.83	D
GERP RS		3.1
PromoterAI		-0.012	Neutral
Varity_R		0.049
gMVP		0.26
Mutation Taster		=94/6	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

dbSNP: rs556362193; hg19: chr10-70587433;