chr10-68827818-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_152709.5(STOX1):c.195G>C(p.Trp65Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 10)
Consequence
STOX1
NM_152709.5 missense
NM_152709.5 missense
Scores
9
6
3
Clinical Significance
Conservation
PhyloP100: 3.06
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STOX1 | NM_152709.5 | c.195G>C | p.Trp65Cys | missense_variant | 1/4 | ENST00000298596.11 | NP_689922.3 | |
STOX1 | NM_001130161.4 | c.195G>C | p.Trp65Cys | missense_variant | 1/5 | NP_001123633.1 | ||
STOX1 | NM_001130159.3 | c.195G>C | p.Trp65Cys | missense_variant | 1/4 | NP_001123631.1 | ||
STOX1 | NM_001130160.3 | c.195G>C | p.Trp65Cys | missense_variant | 1/3 | NP_001123632.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STOX1 | ENST00000298596.11 | c.195G>C | p.Trp65Cys | missense_variant | 1/4 | 1 | NM_152709.5 | ENSP00000298596 | P4 |
Frequencies
GnomAD3 genomes Cov.: 10
GnomAD3 genomes
Cov.:
10
GnomAD4 exome Cov.: 6
GnomAD4 exome
Cov.:
6
GnomAD4 genome Cov.: 10
GnomAD4 genome
Cov.:
10
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2022 | The c.195G>C (p.W65C) alteration is located in exon 1 (coding exon 1) of the STOX1 gene. This alteration results from a G to C substitution at nucleotide position 195, causing the tryptophan (W) at amino acid position 65 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M;M
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Pathogenic
D;D;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;D;D
Sift4G
Pathogenic
D;D;.;D;D
Polyphen
D;D;.;D;D
Vest4
MutPred
Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);Gain of disorder (P = 0.0222);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at