rs3125630

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001048166.1(STIL):c.257C>T(p.Ala86Val) variant causes a missense change. The variant allele was found at a frequency of 0.501 in 1,606,720 control chromosomes in the GnomAD database, including 208,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27290 hom., cov: 32)

Exomes 𝑓: 0.49 ( 181655 hom. )

Consequence

STIL
NM_001048166.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 5.35

Publications

47 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive primary microcephaly
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
microcephaly 7, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

STIL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.9604446E-7).

BP6

Variant 1-47302242-G-A is Benign according to our data. Variant chr1-47302242-G-A is described in ClinVar as Benign. ClinVar VariationId is 21354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1 link	c.257C>T	p.Ala86Val	missense_variant	Exon 4 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.257C>T	p.Ala86Val	missense_variant	Exon 4 of 17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87330

AN:

151862

Hom.:

27255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.539

GnomAD2 exomes

AF:

0.498

AC:

125160

AN:

251140

AF XY:

0.488

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.494

AC:

718056

AN:

1454740

Hom.:

181655

Cov.:

AF XY:

0.490

AC XY:

355055

AN XY:

724056

show subpopulations

African (AFR)

AF:

0.849

AC:

28288

AN:

33328

American (AMR)

AF:

0.557

AC:

24889

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

9259

AN:

26086

East Asian (EAS)

AF:

0.581

AC:

23053

AN:

39650

South Asian (SAS)

AF:

0.464

AC:

39931

AN:

86088

European-Finnish (FIN)

AF:

0.362

AC:

19312

AN:

53370

Middle Eastern (MID)

AF:

0.473

AC:

2719

AN:

5746

European-Non Finnish (NFE)

AF:

0.489

AC:

540725

AN:

1105616

Other (OTH)

AF:

0.497

AC:

29880

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

17461

34922

52384

69845

87306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16036

32072

48108

64144

80180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.575

AC:

87411

AN:

151980

Hom.:

27290

Cov.:

AF XY:

0.569

AC XY:

42257

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.831

AC:

34487

AN:

41480

American (AMR)

AF:

0.569

AC:

8676

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1183

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2854

AN:

5164

South Asian (SAS)

AF:

0.449

AC:

2159

AN:

4812

European-Finnish (FIN)

AF:

0.355

AC:

3750

AN:

10550

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32556

AN:

67956

Other (OTH)

AF:

0.536

AC:

1128

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1676

3352

5028

6704

8380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.511

Hom.:

71373

Bravo

AF:

0.605

TwinsUK

AF:

0.488

AC:

1809

ALSPAC

AF:

0.492

AC:

1895

ESP6500AA

AF:

0.820

AC:

3612

ESP6500EA

AF:

0.477

AC:

4102

ExAC

AF:

0.502

AC:

60992

Asia WGS

AF:

0.508

AC:

1770

AN:

3478

EpiCase

AF:

0.471

EpiControl

AF:

0.474

ClinVar

Significance: Benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 7, primary, autosomal recessive

Benign:4Other:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.099

T;.;.;.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.078

T;T;T;T;T;T

MetaRNN

Benign

6.0e-7

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.9

N;.;N;.;.;.

PhyloP100

5.4

PrimateAI

Benign

0.34

PROVEAN

Benign

3.1

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.;.

Polyphen

0.0

B;.;B;B;B;.

Vest4

0.14

MPC

0.10

ClinPred

0.011

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over