10-92653751-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004523.4(KIF11):c.3126G>C(p.Leu1042Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,613,806 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 38 hom. )

Consequence

KIF11
NM_004523.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.236

Publications

5 publications found

Variant links:

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

KIF11 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=0.002524376).

BP6

Variant 10-92653751-G-C is Benign according to our data. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92653751-G-C is described in CliVar as Benign/Likely_benign. Clinvar id is 235554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1990/152226) while in subpopulation AFR AF = 0.0444 (1844/41526). AF 95% confidence interval is 0.0427. There are 49 homozygotes in GnomAd4. There are 952 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1990 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.3126G>C	p.Leu1042Phe	missense_variant	Exon 22 of 22	ENST00000260731.5	NP_004514.2	P52732

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5 link	c.3126G>C	p.Leu1042Phe	missense_variant	Exon 22 of 22	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1989

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00352

AC:

884

AN:

251448

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00146

AC:

2141

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

951

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0450

AC:

1507

AN:

33458

American (AMR)

AF:

0.00291

AC:

130

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000151

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000241

AC:

268

AN:

1111768

Other (OTH)

AF:

0.00339

AC:

205

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

190

284

379

474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0131

AC:

1990

AN:

152226

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

952

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0444

AC:

1844

AN:

41526

American (AMR)

AF:

0.00595

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68026

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

194

291

388

485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00212

Hom.:

Bravo

AF:

0.0139

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0395

AC:

174

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00443

AC:

538

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Dec 10, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Oct 28, 2015

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

Benign:1

Jul 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.12

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.099

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.24

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.48

REVEL

Benign

0.041

Sift

Benign

0.13

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.048

MutPred

0.12

Loss of disorder (P = 0.0861);

MVP

0.16

MPC

0.32

ClinPred

0.0029

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.060

Mutation Taster

=100/0

polymorphism

(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