Genetic Variant KIF6:p.Trp719Arg (chr6-39357302-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145027.6(KIF6):c.2155T>A(p.Trp719Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIF6
NM_145027.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029600948).

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.2155T>A	p.Trp719Arg	missense	Exon 19 of 23	NP_659464.3
KIF6	NM_001289020.3		c.2104T>A	p.Trp702Arg	missense	Exon 18 of 22	NP_001275949.1
KIF6	NM_001289021.3		c.1987T>A	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>A	p.Trp719Arg	missense	Exon 19 of 23	ENSP00000287152.7	Q6ZMV9-1
KIF6	ENST00000458470.5	TSL:1	c.1828T>A	p.Trp610Arg	missense	Exon 16 of 19	ENSP00000409417.1	H0Y718
KIF6	ENST00000229913.9	TSL:1	c.508T>A	p.Trp170Arg	missense	Exon 6 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726934

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111432

Other (OTH)

AF:

0.00

AC:

AN:

60380

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.0

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.032

M_CAP

Benign

0.0077

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

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

Polyphen

0.0

Vest4

0.016

MutPred

0.087

Gain of solvent accessibility (P = 0.0584)

MVP

0.41

MPC

0.11

ClinPred

0.048

GERP RS

0.53

Varity_R

0.051

gMVP

0.28

Mutation Taster

=99/1

polymorphism

(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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over