NM_152709.5:c.185T>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STOX1	NM_152709.5	c.185T>C	p.Phe62Ser	missense_variant	Exon 1 of 4	ENST00000298596.11	NP_689922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STOX1	ENST00000298596.11	c.185T>C	p.Phe62Ser	missense_variant	Exon 1 of 4	1	NM_152709.5	ENSP00000298596.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185T>C (p.F62S) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a T to C substitution at nucleotide position 185, causing the phenylalanine (F) at amino acid position 62 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.43	.;T;T;T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.5	M;M;.;M;M
PROVEAN	Uncertain	-3.3	D;D;.;D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D;.;T;D
Sift4G	Uncertain	0.0030	D;D;.;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.79
MutPred		0.63		Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);
MVP		0.78
MPC		0.53
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.61
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-70587565;