rs13289566

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.1973G>A(p.Gly658Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,604,476 control chromosomes in the GnomAD database, including 30,432 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 0.21 ( 3509 hom., cov: 31)

Exomes 𝑓: 0.20 ( 26923 hom. )

Consequence

KIF27
NM_017576.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0480

Publications

22 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:

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=0.0023303032).

BP6

Variant 9-83889090-C-T is Benign according to our data. Variant chr9-83889090-C-T is described in ClinVar as Benign. ClinVar VariationId is 403015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.1973G>A	p.Gly658Glu	missense_variant	Exon 7 of 18	ENST00000297814.7	NP_060046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KIF27	ENST00000297814.7 link	c.1973G>A	p.Gly658Glu	missense_variant	Exon 7 of 18	1	NM_017576.4	ENSP00000297814.2
KIF27	ENST00000413982.5 link	c.1973G>A	p.Gly658Glu	missense_variant	Exon 7 of 17	1		ENSP00000401688.1
KIF27	ENST00000334204.6 link	c.1973G>A	p.Gly658Glu	missense_variant	Exon 7 of 16	1		ENSP00000333928.2
KIF27	ENST00000376347.1 link	c.146G>A	p.Gly49Glu	missense_variant	Exon 1 of 5	5		ENSP00000365525.1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32044

AN:

151600

Hom.:

3512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.00134

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.217

GnomAD2 exomes

AF:

0.191

AC:

47664

AN:

249340

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.000545

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.204

AC:

296461

AN:

1452758

Hom.:

26923

Cov.:

AF XY:

0.206

AC XY:

148918

AN XY:

722944

show subpopulations

African (AFR)

AF:

0.231

AC:

7674

AN:

33162

American (AMR)

AF:

0.108

AC:

4803

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5354

AN:

25962

East Asian (EAS)

AF:

0.000479

AC:

AN:

39670

South Asian (SAS)

AF:

0.234

AC:

20029

AN:

85448

European-Finnish (FIN)

AF:

0.210

AC:

11154

AN:

53202

Middle Eastern (MID)

AF:

0.267

AC:

1532

AN:

5746

European-Non Finnish (NFE)

AF:

0.212

AC:

233782

AN:

1104964

Other (OTH)

AF:

0.202

AC:

12114

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

10740

21479

32219

42958

53698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8058

16116

24174

32232

40290

<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:

0.211

AC:

32047

AN:

151718

Hom.:

3509

Cov.:

AF XY:

0.211

AC XY:

15645

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.243

AC:

10018

AN:

41206

American (AMR)

AF:

0.158

AC:

2412

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

704

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5194

South Asian (SAS)

AF:

0.207

AC:

999

AN:

4816

European-Finnish (FIN)

AF:

0.211

AC:

2228

AN:

10542

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.221

AC:

15016

AN:

67934

Other (OTH)

AF:

0.214

AC:

450

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1241

2482

3724

4965

6206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.220

Hom.:

1590

Bravo

AF:

0.207

TwinsUK

AF:

0.217

AC:

805

ALSPAC

AF:

0.207

AC:

799

ESP6500AA

AF:

0.250

AC:

1101

ESP6500EA

AF:

0.217

AC:

1869

ExAC

AF:

0.200

AC:

24236

Asia WGS

AF:

0.0940

AC:

327

AN:

3476

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

0.063

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0028

T;.;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.68

T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.29

N;N;N;.

PhyloP100

0.048

PrimateAI

Benign

0.27

PROVEAN

Benign

0.080

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.045

MPC

0.076

ClinPred

0.000014

GERP RS

0.39

PromoterAI

-0.0019

Neutral

(source)

Varity_R

0.046

gMVP

0.068

Mutation Taster

=100/0

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