Variant rs58077086 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

ENSG00000231616 (HGNC:):

ENSG00000231616 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=0.0017277896).

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/exons	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.3439A>G	p.Met1147Val	missense_variant	16/18	ENST00000297814.7	NP_060046.1	Q86VH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF27	ENST00000297814.7 link	c.3439A>G	p.Met1147Val	missense_variant	16/18	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

GnomAD3 exomes

AF:

0.199

AC:

49852

AN:

251066

Hom.:

5449

AF XY:

0.202

AC XY:

27428

AN XY:

135694

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 SAS exome

AF:

0.172

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

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.175

AC:

26635

AN:

152196

Hom.:

2906

Cov.:

AF XY:

0.172

AC XY:

12781

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0528

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.225

Hom.:

1301

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

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

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.2

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;.;.

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

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