dbSNP rs142601912: KIF11:p.Val627Ile (chr10-92637187-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004523.4(KIF11):c.1879G>A(p.Val627Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V627L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

KIF11
NM_004523.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091977775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.1879G>A	p.Val627Ile	missense_variant	Exon 15 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.1879G>A	p.Val627Ile	missense_variant	Exon 15 of 22	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426854

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30742

American (AMR)

AF:

0.00

AC:

AN:

32784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24828

East Asian (EAS)

AF:

0.00

AC:

AN:

38774

South Asian (SAS)

AF:

0.00

AC:

AN:

80228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52792

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102402

Other (OTH)

AF:

0.00

AC:

AN:

58912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

Uncertain:1

May 24, 2021

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.12

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.51

M_CAP

Benign

0.0096

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

1.8

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.34

REVEL

Benign

0.063

Sift

Benign

0.17

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.085

MutPred

0.29

Gain of catalytic residue at L632 (P = 0.0471);

MVP

0.28

MPC

0.24

ClinPred

0.18

GERP RS

1.3

Varity_R

0.020

gMVP

0.18

Mutation Taster

=99/1

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over