rs201354921
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001048166.1(STIL):c.3157G>A(p.Gly1053Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000097 in 1,607,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000094 ( 0 hom. )
Consequence
STIL
NM_001048166.1 missense
NM_001048166.1 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
STIL (HGNC:10879): (STIL centriolar assembly protein) This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint. It is proposed to regulate Cdc2 kinase activity during spindle checkpoint arrest. Chromosomal deletions that fuse this gene and the adjacent locus commonly occur in T cell leukemias, and are thought to arise through illegitimate V-(D)-J recombination events. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13432622).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STIL | NM_001048166.1 | c.3157G>A | p.Gly1053Ser | missense_variant | 17/17 | ENST00000371877.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STIL | ENST00000371877.8 | c.3157G>A | p.Gly1053Ser | missense_variant | 17/17 | 1 | NM_001048166.1 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152146Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000739 AC: 18AN: 243496Hom.: 0 AF XY: 0.000114 AC XY: 15AN XY: 131608
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GnomAD4 exome AF: 0.0000941 AC: 137AN: 1455218Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 76AN XY: 723560
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GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74456
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microcephaly 7, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 17, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 22, 2023 | This variant has not been reported in the literature in individuals affected with STIL-related conditions. This variant is present in population databases (rs201354921, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1052 of the STIL protein (p.Gly1052Ser). ClinVar contains an entry for this variant (Variation ID: 160062). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STIL protein function. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;N;N
REVEL
Benign
Sift
Benign
T;D;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;.;D;D
Vest4
MutPred
Loss of glycosylation at S1051 (P = 0.0602);.;.;.;
MVP
MPC
0.40
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at