Genetic Variant NM_145027.6:c.1919G>A (chr6-39362461-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145027.6(KIF6):c.1919G>A(p.Arg640Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

KIF6
NM_145027.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Publications

0 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:

LOC107986594 (HGNC:):

LOC107986594 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20518667).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIF6	NM_145027.6	MANE Select	c.1919G>A	p.Arg640Gln	missense	Exon 17 of 23	NP_659464.3
KIF6	NM_001289020.3		c.1868G>A	p.Arg623Gln	missense	Exon 16 of 22	NP_001275949.1
KIF6	NM_001289021.3		c.1751G>A	p.Arg584Gln	missense	Exon 16 of 22	NP_001275950.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF6	ENST00000287152.12	TSL:2 MANE Select	c.1919G>A	p.Arg640Gln	missense	Exon 17 of 23	ENSP00000287152.7	Q6ZMV9-1
KIF6	ENST00000458470.5	TSL:1	c.1592G>A	p.Arg531Gln	missense	Exon 14 of 19	ENSP00000409417.1	H0Y718
KIF6	ENST00000229913.9	TSL:1	c.272G>A	p.Arg91Gln	missense	Exon 4 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000636

AC:

AN:

251492

AF XY:

0.0000441

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111928

Other (OTH)

AF:

0.000116

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41550

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000579

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.025

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

PhyloP100

5.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.33

Polyphen

1.0

Vest4

0.55

MVP

0.52

MPC

0.32

ClinPred

0.28

GERP RS

5.2

Varity_R

0.20

gMVP

0.19

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over