rs55654273

Variant names:

Variant summary

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

The NM_017576.4(KIF27):c.3106A>G(p.Asn1036Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,412 control chromosomes in the GnomAD database, including 14,901 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1036S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.13 ( 1458 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13443 hom. )

Consequence

KIF27
NM_017576.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.06

Publications

13 publications found

Variant links:

Genes affected

KIF27 (HGNC:18632): (kinesin family member 27) This gene is a member of the KIF27 (kinesin 4) sub-family of the mammalian kinesin family. The gene is an ortholog of the Drosophila Cos2 gene, which plays an important role in the Hedgehog signaling pathway. The encoded protein contains an N-terminal motor domain which includes nucleotide-binding and microtubule-interacting regions, a stalk domain containing a predicted coiled coil motif and a C-terminal tail domain. Alternatively spliced transcript variants have been observed for this gene. Pseudogenes associated with this gene are located on chromosome 9. [provided by RefSeq, Dec 2012]

KIF27 links:

ENSG00000226877 (HGNC:):

ENSG00000226877 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=0.0038152337).

BP6

Variant 9-83859200-T-C is Benign according to our data. Variant chr9-83859200-T-C is described in ClinVar as Benign. ClinVar VariationId is 403013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.3106A>G	p.Asn1036Asp	missense_variant	Exon 14 of 18	ENST00000297814.7	NP_060046.1	Q86VH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF27	ENST00000297814.7 link	c.3106A>G	p.Asn1036Asp	missense_variant	Exon 14 of 18	1	NM_017576.4	ENSP00000297814.2		Q86VH2-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20339

AN:

152136

Hom.:

1451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0925

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.122

AC:

30733

AN:

251410

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0988

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.133

AC:

194067

AN:

1461158

Hom.:

13443

Cov.:

AF XY:

0.131

AC XY:

95565

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.142

AC:

4753

AN:

33446

American (AMR)

AF:

0.0806

AC:

3604

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2873

AN:

26126

East Asian (EAS)

AF:

0.0991

AC:

3932

AN:

39676

South Asian (SAS)

AF:

0.0939

AC:

8097

AN:

86246

European-Finnish (FIN)

AF:

0.164

AC:

8748

AN:

53412

Middle Eastern (MID)

AF:

0.0553

AC:

319

AN:

5768

European-Non Finnish (NFE)

AF:

0.139

AC:

154031

AN:

1111388

Other (OTH)

AF:

0.128

AC:

7710

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

8800

17599

26399

35198

43998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5450

10900

16350

21800

27250

<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:

0.134

AC:

20378

AN:

152254

Hom.:

1458

Cov.:

AF XY:

0.133

AC XY:

9935

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.143

AC:

5956

AN:

41556

American (AMR)

AF:

0.0924

AC:

1414

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

386

AN:

3470

East Asian (EAS)

AF:

0.105

AC:

543

AN:

5182

South Asian (SAS)

AF:

0.0939

AC:

453

AN:

4826

European-Finnish (FIN)

AF:

0.165

AC:

1752

AN:

10604

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9486

AN:

68004

Other (OTH)

AF:

0.114

AC:

241

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

908

1815

2723

3630

4538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.135

Hom.:

3159

Bravo

AF:

0.129

TwinsUK

AF:

0.135

AC:

499

ALSPAC

AF:

0.134

AC:

517

ESP6500AA

AF:

0.146

AC:

642

ESP6500EA

AF:

0.137

AC:

1182

ExAC

AF:

0.123

AC:

14904

Asia WGS

AF:

0.100

AC:

349

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.127

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0016

T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.068

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PhyloP100

2.1

PrimateAI

Benign

0.36

PROVEAN

Benign

0.40

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.020

B;B;B

Vest4

0.048

MPC

0.63

ClinPred

0.0013

GERP RS

4.5

Varity_R

0.11

gMVP

0.069

Mutation Taster

=97/3

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