rs1487657280

Variant names:

• chr10-68827678-C-A
• rs1487657280
• NM_152709.5:c.55C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-68827678-C-A
• chr10-68827678-C-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.55C>A​(p.Leu19Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STOX1 NM_152709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• 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=0.298171).

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.55C>A	p.Leu19Met	missense	Exon 1 of 4	NP_689922.3
	STOX1	NM_001130161.4		c.55C>A	p.Leu19Met	missense	Exon 1 of 5	NP_001123633.1	Q6ZVD7-1
	STOX1	NM_001130159.3		c.55C>A	p.Leu19Met	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.55C>A	p.Leu19Met	missense	Exon 1 of 4	ENSP00000298596.6	Q6ZVD7-1
	STOX1	ENST00000399169.8	TSL:1	c.55C>A	p.Leu19Met	missense	Exon 1 of 5	ENSP00000382121.4	Q6ZVD7-1
	STOX1	ENST00000399165.8	TSL:1	c.55C>A	p.Leu19Met	missense	Exon 1 of 4	ENSP00000382118.4	Q6ZVD7-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00 AC: 0 AN: 856 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000103 AC: 1 AN: 970712 Hom.: 0 Cov.: 24 AF XY: 0.00000219 AC XY: 1 AN XY: 457246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18996

American (AMR) AF: 0.00 AC: 0 AN: 5326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9884

East Asian (EAS) AF: 0.00 AC: 0 AN: 16576

South Asian (SAS) AF: 0.00 AC: 0 AN: 18742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2348

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 846994

Other (OTH) AF: 0.00 AC: 0 AN: 35958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.13
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.25	T
Polyphen		0.13	B
Vest4		0.20
MutPred		0.36		Gain of catalytic residue at L19 (P = 0.0031)
MVP		0.47
MPC		0.25
ClinPred		0.22	T
GERP RS		0.71
PromoterAI		0.14	Neutral
Varity_R		0.10
gMVP		0.071
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1487657280; hg19: chr10-70587435;