rs587784449

Variant names:

• chr1-47269708-C-A
• NM_001048166.1:c.2542G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-47269708-C-A
• chr1-47269708-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001048166.1(STIL):​c.2542G>T​(p.Val848Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V848I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STIL NM_001048166.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1	c.2542G>T	p.Val848Phe	missense_variant	Exon 14 of 17	ENST00000371877.8	NP_001041631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIL	ENST00000371877.8	c.2542G>T	p.Val848Phe	missense_variant	Exon 14 of 17	1	NM_001048166.1	ENSP00000360944.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.7	M;.;M;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N;.;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;.;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;.
Polyphen		0.99	D;.;D;D;D
Vest4		0.77
MutPred		0.12		Loss of sheet (P = 0.0142);.;Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);.;
MVP		0.83
MPC		0.57
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.32
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr1-47735380;