dbSNP rs796052144: KIF11:p.Asp69Asn (chr10-92606392-G-A) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6

The NM_004523.4(KIF11):c.205G>A(p.Asp69Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D69A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF11
NM_004523.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 8.78

Publications

1 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 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

BP6

Variant 10-92606392-G-A is Benign according to our data. Variant chr10-92606392-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 207836.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.205G>A	p.Asp69Asn	missense_variant	Exon 2 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.205G>A	p.Asp69Asn	missense_variant	Exon 2 of 22	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32898

American (AMR)

AF:

0.00

AC:

AN:

41362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

83724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108830

Other (OTH)

AF:

0.00

AC:

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Medical Research Institute, Tokyo Medical and Dental University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.69

MutationAssessor

Pathogenic

3.1

PhyloP100

8.8

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.74

Sift

Benign

0.081

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MutPred

0.95

Loss of ubiquitination at K64 (P = 0.0413);

MVP

0.90

MPC

2.2

ClinPred

1.0

GERP RS

5.9

Varity_R

0.77

gMVP

0.91

Mutation Taster

=23/77

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over