Variant 6-39343778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_145027.6(KIF6):c.2359G>A(p.Gly787Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00387 in 1,612,614 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 20 hom. )

Consequence

KIF6
NM_145027.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.19

Variant links:

Genes affected

KIF6 (HGNC:21202): (kinesin family member 6) This gene encodes a member of a family of molecular motors which are involved in intracellular transport of protein complexes, membrane organelles, and messenger ribonucleic acid along microtubules. Kinesins function as homodimeric molecules with two N-terminal head domains that move along microtubules and two C-terminal tail domains that interact with the transported cargo, either directly or indirectly, through adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissue. A naturally occurring mutation in this gene is associated with coronary heart disease. [provided by RefSeq, May 2017]

KIF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031724036).

BP6

Variant 6-39343778-C-T is Benign according to our data. Variant chr6-39343778-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056494.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF6	NM_145027.6 link	c.2359G>A	p.Gly787Arg	missense_variant	22/23	ENST00000287152.12	NP_659464.3	Q6ZMV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF6	ENST00000287152.12 link	c.2359G>A	p.Gly787Arg	missense_variant	22/23	2	NM_145027.6	ENSP00000287152.7		Q6ZMV9-1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00482

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00212

AC:

529

AN:

249594

Hom.:

AF XY:

0.00210

AC XY:

283

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.000790

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.00397

AC:

5792

AN:

1460290

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

2761

AN XY:

726402

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.000811

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00293

AC:

447

AN:

152324

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00482

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00212

AC:

257

EpiCase

AF:

0.00409

EpiControl

AF:

0.00452

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIF6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.062

T;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.4

M;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.4

D;D;D;.

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.59

MutPred

0.26

Gain of phosphorylation at S789 (P = 0.0859);.;.;.;

MVP

0.96

MPC

0.42

ClinPred

0.039

GERP RS

4.9

Varity_R

0.54

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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