rs20455

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -5 classification points (ACGS-UK Somatic Oncogenicity v2025): 0P and 5B. B1_StrongB3_Supporting

The NM_145027.6(KIF6):c.2155T>C (p.Trp719Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.386 (AC=622,475) in the gnomAD database across 1,611,174 control chromosomes, including 129,068 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.803. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★★★). The variant has been observed in cBioPortal in 3 samples across 3 studies and 3 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

Frequency

Genomes: 𝑓 0.49 ( 21098 hom., cov: 31)

Exomes 𝑓: 0.38 ( 107970 hom. )

Consequence

KIF6
NM_145027.6 missense

Scores

Clinical Significance

drug response reviewed by expert panel O:1

Conservation

PhyloP100: 0.0610

Publications

136 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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: LiferaOmics

KIF6 links:

LOC107986594 (HGNC:):

LOC107986594 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_145027.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.803 — exceeds 1% threshold (B1 applied)

Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIF6	NM_145027.6	MANE Select	c.2155T>C	p.Trp719Arg	missense	Exon 19 of 23	NP_659464.3
KIF6	NM_001289020.3		c.2104T>C	p.Trp702Arg	missense	Exon 18 of 22	NP_001275949.1
KIF6	NM_001289021.3		c.1987T>C	p.Trp663Arg	missense	Exon 18 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.2155T>C	p.Trp719Arg	missense	Exon 19 of 23	ENSP00000287152.7	Q6ZMV9-1
KIF6	ENST00000458470.5	TSL:1	c.1828T>C	p.Trp610Arg	missense	Exon 16 of 19	ENSP00000409417.1	H0Y718
KIF6	ENST00000229913.9	TSL:1	c.508T>C	p.Trp170Arg	missense	Exon 6 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74283

AN:

151892

Hom.:

21067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.798

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.405

AC:

101846

AN:

251262

AF XY:

0.400

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.376

AC:

548109

AN:

1459164

Hom.:

107970

Cov.:

AF XY:

0.376

AC XY:

273110

AN XY:

726034

show subpopulations

African (AFR)

AF:

0.811

AC:

27109

AN:

33412

American (AMR)

AF:

0.344

AC:

15356

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

8875

AN:

26120

East Asian (EAS)

AF:

0.477

AC:

18909

AN:

39680

South Asian (SAS)

AF:

0.428

AC:

36887

AN:

86146

European-Finnish (FIN)

AF:

0.345

AC:

18432

AN:

53396

Middle Eastern (MID)

AF:

0.414

AC:

2387

AN:

5764

European-Non Finnish (NFE)

AF:

0.357

AC:

395811

AN:

1109676

Other (OTH)

AF:

0.404

AC:

24343

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14930

29860

44790

59720

74650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12754

25508

38262

51016

63770

<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:

0.489

AC:

74366

AN:

152010

Hom.:

21098

Cov.:

AF XY:

0.485

AC XY:

36000

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.798

AC:

33085

AN:

41462

American (AMR)

AF:

0.385

AC:

5875

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1176

AN:

3472

East Asian (EAS)

AF:

0.477

AC:

2454

AN:

5142

South Asian (SAS)

AF:

0.445

AC:

2143

AN:

4818

European-Finnish (FIN)

AF:

0.347

AC:

3667

AN:

10578

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24541

AN:

67962

Other (OTH)

AF:

0.470

AC:

992

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1661

3323

4984

6646

8307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.424

Hom.:

38444

Bravo

AF:

0.504

Asia WGS

AF:

0.512

AC:

1782

AN:

3478

EpiCase

AF:

0.368

EpiControl

AF:

0.371

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.490

AC:

60123

AN:

122746

Turkish Variome

AF:

0.371

AC:

2485

AN:

6698

Hom.:

481

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.460

AC:

4124

AN:

8960

Hom.:

946

ABraOM SABE-WGS-1171

AF:

0.453

AC:

1060

AN:

2342

Hom.:

253

ClinVar

ClinVar submissions

Significance:drug response

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

pravastatin response - Efficacy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.0

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00095

LIST_S2

Benign

0.032

MetaRNN

Benign

8.2e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.81

PhyloP100

0.061

PrimateAI

Benign

0.17

PROVEAN

Benign

1.5

REVEL

Benign

0.23

Sift

Benign

0.69

Sift4G

Benign

0.36

Varity_R

0.051

gMVP

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over