chr10-68827676-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152709.5(STOX1):​c.53G>C​(p.Arg18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,121,884 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). 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: 𝑓 0.0039 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0062 (30 hom.)
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008164227).
• BP6: Variant 10-68827676-G-C is Benign according to our data. Variant chr10-68827676-G-C is described in ClinVar as Benign. ClinVar VariationId is 3341721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 30 AR gene

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>C	p.Arg18Pro	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.53G>C	p.Arg18Pro	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.53G>C	p.Arg18Pro	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>C	p.Arg18Pro	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.53G>C	p.Arg18Pro	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.53G>C	p.Arg18Pro	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 572 AN: 147280 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00337

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00735

Gnomad OTH AF: 0.00197

GnomAD2 exomes AF: 0.0102 AC: 9 AN: 884 AF XY: 0.0133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00619 AC: 6029 AN: 974500 Hom.: 30 Cov.: 24 AF XY: 0.00622 AC XY: 2853 AN XY: 458920

African (AFR) AF: 0.000367 AC: 7 AN: 19074

American (AMR) AF: 0.000748 AC: 4 AN: 5348

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 16670

South Asian (SAS) AF: 0.0000531 AC: 1 AN: 18822

European-Finnish (FIN) AF: 0.00457 AC: 73 AN: 15958

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

European-Non Finnish (NFE) AF: 0.00682 AC: 5799 AN: 850208

Other (OTH) AF: 0.00401 AC: 145 AN: 36124

GnomAD4 genome AF: 0.00388 AC: 572 AN: 147384 Hom.: 1 Cov.: 29 AF XY: 0.00344 AC XY: 247 AN XY: 71786

African (AFR) AF: 0.00117 AC: 48 AN: 40916

American (AMR) AF: 0.000268 AC: 4 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00337 AC: 31 AN: 9190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00735 AC: 485 AN: 66006

Other (OTH) AF: 0.00195 AC: 4 AN: 2054

Alfa AF: 0.00336 Hom.: 1

Bravo AF: 0.00335

ExAC AF: 0.000437 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Uncertain	0.10
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.0082	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.41	N
PhyloP100		2.2
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.47
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.056	B
Vest4		0.35
MPC		0.10
ClinPred		0.050	T
GERP RS		3.1
PromoterAI		-0.0085	Neutral
Varity_R		0.32
gMVP		0.49
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

dbSNP: rs556362193; hg19: chr10-70587433;