rs141678367

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001048166.1(STIL):c.1055G>A(p.Arg352His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000826 in 1,613,536 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

STIL
NM_001048166.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.157

Variant links:

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]

STIL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007013947).

BP6

Variant 1-47287629-C-T is Benign according to our data. Variant chr1-47287629-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235445.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=3, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00304 (463/152230) while in subpopulation AFR AF= 0.00989 (411/41542). AF 95% confidence interval is 0.0091. There are 2 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1 link	c.1055G>A	p.Arg352His	missense_variant	Exon 10 of 17	ENST00000371877.8	NP_001041631.1	Q15468-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIL	ENST00000371877.8 link	c.1055G>A	p.Arg352His	missense_variant	Exon 10 of 17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

463

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00992

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.000832

AC:

209

AN:

251274

Hom.:

AF XY:

0.000626

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000595

AC:

869

AN:

1461306

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

398

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.00304

AC:

463

AN:

152230

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00989

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.000667

Hom.:

Bravo

AF:

0.00331

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000980

AC:

119

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000328

EpiControl

AF:

0.000415

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STIL: BP4, BS2 -

Oct 28, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 22, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23772360) -

not specified

Benign:2

Aug 19, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 17, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly 7, primary, autosomal recessive

Uncertain:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.5

DANN

Benign

0.24

DEOGEN2

Benign

0.080

T;.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.48

T;T;T;T;T

MetaRNN

Benign

0.0070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.;N;.;.

PrimateAI

Benign

0.17

PROVEAN

Benign

0.66

N;.;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.65

T;.;T;T;T

Sift4G

Benign

0.35

T;T;T;T;.

Polyphen

0.0

B;.;B;B;B

Vest4

0.10

MVP

0.38

MPC

0.13

ClinPred

0.0018

GERP RS

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.018

gMVP

0.088

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over