rs12001918

Positions:

chr9-83903881-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000297814.7(KIF27):c.637A>G(p.Ile213Val) 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 1,613,850 control chromosomes in the GnomAD database, including 14,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1444 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13286 hom. )

Consequence

KIF27
ENST00000297814.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.16

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00205189).

BP6

Variant 9-83903881-T-C is Benign according to our data. Variant chr9-83903881-T-C is described in ClinVar as [Benign]. Clinvar id is 403016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF27	NM_017576.4 linkuse as main transcript	c.637A>G	p.Ile213Val	missense_variant	4/18	ENST00000297814.7	NP_060046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF27	ENST00000297814.7 linkuse as main transcript	c.637A>G	p.Ile213Val	missense_variant	4/18	1	NM_017576.4	ENSP00000297814	P1	Q86VH2-1
KIF27	ENST00000413982.5 linkuse as main transcript	c.637A>G	p.Ile213Val	missense_variant	4/17	1		ENSP00000401688		Q86VH2-2
KIF27	ENST00000334204.6 linkuse as main transcript	c.637A>G	p.Ile213Val	missense_variant	4/16	1		ENSP00000333928		Q86VH2-3
KIF27	ENST00000495062.2 linkuse as main transcript	c.500-4077A>G		intron_variant, NMD_transcript_variant		5		ENSP00000431390

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20309

AN:

152032

Hom.:

1437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0923

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0934

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.122

AC:

30685

AN:

251380

Hom.:

2014

AF XY:

0.121

AC XY:

16507

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.0988

Gnomad SAS exome

AF:

0.0960

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.133

AC:

193915

AN:

1461700

Hom.:

13286

Cov.:

AF XY:

0.131

AC XY:

95505

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.0806

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0994

Gnomad4 SAS exome

AF:

0.0942

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.134

AC:

20348

AN:

152150

Hom.:

1444

Cov.:

AF XY:

0.133

AC XY:

9916

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0922

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0948

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.133

Hom.:

3518

Bravo

AF:

0.129

TwinsUK

AF:

0.134

AC:

498

ALSPAC

AF:

0.134

AC:

518

ESP6500AA

AF:

0.146

AC:

644

ESP6500EA

AF:

0.137

AC:

1181

ExAC

AF:

0.123

AC:

14880

Asia WGS

AF:

0.100

AC:

350

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.099

T;.;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.36

N;N;N

MutationTaster

Benign

0.17

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.68

T;T;T

Sift4G

Benign

0.71

T;T;T

Polyphen

0.79

P;P;B

Vest4

0.15

MPC

0.15

ClinPred

0.019

GERP RS

4.4

Varity_R

0.067

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over