rs58077086

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.3439A>G(p.Met1147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,611,616 control chromosomes in the GnomAD database, including 42,729 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 Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2906 hom., cov: 31)

Exomes 𝑓: 0.23 ( 39823 hom. )

Consequence

KIF27
NM_017576.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.266

Publications

15 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=0.0017277896).

BP6

Variant 9-83850216-T-C is Benign according to our data. Variant chr9-83850216-T-C is described in ClinVar as [Benign]. Clinvar id is 403011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.3439A>G	p.Met1147Val	missense_variant	Exon 16 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.3439A>G	p.Met1147Val	missense_variant	Exon 16 of 18	1	NM_017576.4	ENSP00000297814.2		Q86VH2-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26623

AN:

152078

Hom.:

2900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.199

AC:

49852

AN:

251066

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.0492

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.229

AC:

334515

AN:

1459420

Hom.:

39823

Cov.:

AF XY:

0.228

AC XY:

165770

AN XY:

726192

show subpopulations

African (AFR)

AF:

0.0470

AC:

1572

AN:

33460

American (AMR)

AF:

0.179

AC:

7995

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6529

AN:

26112

East Asian (EAS)

AF:

0.120

AC:

4753

AN:

39688

South Asian (SAS)

AF:

0.173

AC:

14883

AN:

86216

European-Finnish (FIN)

AF:

0.209

AC:

11158

AN:

53420

Middle Eastern (MID)

AF:

0.233

AC:

1343

AN:

5754

European-Non Finnish (NFE)

AF:

0.246

AC:

273240

AN:

1109786

Other (OTH)

AF:

0.216

AC:

13042

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12748

25496

38243

50991

63739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9154

18308

27462

36616

45770

<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:

0.175

AC:

26635

AN:

152196

Hom.:

2906

Cov.:

AF XY:

0.172

AC XY:

12781

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0528

AC:

2197

AN:

41582

American (AMR)

AF:

0.196

AC:

2990

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3464

East Asian (EAS)

AF:

0.108

AC:

558

AN:

5184

South Asian (SAS)

AF:

0.165

AC:

793

AN:

4818

European-Finnish (FIN)

AF:

0.202

AC:

2140

AN:

10578

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16342

AN:

67976

Other (OTH)

AF:

0.190

AC:

401

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1082

2163

3245

4326

5408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.222

Hom.:

1303

Bravo

AF:

0.170

ESP6500AA

AF:

0.0563

AC:

248

ESP6500EA

AF:

0.241

AC:

2071

ExAC

AF:

0.196

AC:

23828

EpiCase

AF:

0.245

EpiControl

AF:

0.245

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

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.2

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0054

T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

PhyloP100

-0.27

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.090

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.034

MPC

0.56

ClinPred

0.0017

GERP RS

-0.82

Varity_R

0.076

gMVP

0.10

Mutation Taster

=99/1

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