chr10-68827676-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 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. 13/20 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. R18P) has been classified as Likely pathogenic.

• 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

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
• BP4: Computational evidence support a benign effect (MetaRNN=0.31576413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5	c.53G>A	p.Arg18Gln	missense_variant	Exon 1 of 4	ENST00000298596.11	NP_689922.3
STOX1	NM_001130161.4	c.53G>A	p.Arg18Gln	missense_variant	Exon 1 of 5		NP_001123633.1
STOX1	NM_001130159.3	c.53G>A	p.Arg18Gln	missense_variant	Exon 1 of 4		NP_001123631.1
STOX1	NM_001130160.3	c.53G>A	p.Arg18Gln	missense_variant	Exon 1 of 3		NP_001123632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.53G>A	p.Arg18Gln	missense_variant	Exon 1 of 4	1	NM_152709.5	ENSP00000298596.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000600

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000470

Gnomad4 OTH exome AF: 0.0000277

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	.;T;T;T;T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.3	L;L;.;L;L
PROVEAN	Benign	-1.3	N;N;.;N;N
REVEL	Benign	0.27
Sift	Benign	0.096	T;T;.;T;T
Sift4G	Benign	0.073	T;T;.;T;T
Polyphen		0.98	D;D;.;D;D
Vest4		0.18
MutPred		0.37		Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);Loss of MoRF binding (P = 0.0658);
MVP		0.80
MPC		0.16
ClinPred		0.83	D
GERP RS		3.1
Varity_R		0.049
gMVP		0.26

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: rs556362193; hg19: chr10-70587433;