Genetic Variant KIF6:p.Gly787Arg (chr6-39343778-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KIF6	NM_145027.6 link	c.2359G>A	p.Gly787Arg	missense_variant	Exon 22 of 23	ENST00000287152.12	NP_659464.3	Q6ZMV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF6	ENST00000287152.12 link	c.2359G>A	p.Gly787Arg	missense_variant	Exon 22 of 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

GnomAD2 exomes

AF:

0.00212

AC:

529

AN:

249594

AF XY:

0.00210

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 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

African (AFR)

AF:

0.000628

AC:

AN:

33418

American (AMR)

AF:

0.000811

AC:

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26070

East Asian (EAS)

AF:

0.000151

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85928

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00476

AC:

5295

AN:

1111396

Other (OTH)

AF:

0.00514

AC:

310

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

254

508

761

1015

1269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00293

AC:

447

AN:

152324

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41578

American (AMR)

AF:

0.00294

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00482

AC:

328

AN:

68032

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00360

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

Feb 10, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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;.;.;.

PhyloP100

4.2

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

Mutation Taster

=88/12

polymorphism

(source)

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

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6-39343778-C-T

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