chr6-39362461-C-A

Variant names:

• chr6-39362461-C-A
• rs188790180
• NM_145027.6:c.1919G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145027.6(KIF6):​c.1919G>T​(p.Arg640Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R640Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF6 NM_145027.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18
• Publications: 0 publications found

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]

LOC107986594 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	NM_145027.6	MANE Select	c.1919G>T	p.Arg640Leu	missense	Exon 17 of 23	NP_659464.3
	KIF6	NM_001289020.3		c.1868G>T	p.Arg623Leu	missense	Exon 16 of 22	NP_001275949.1
	KIF6	NM_001289021.3		c.1751G>T	p.Arg584Leu	missense	Exon 16 of 22	NP_001275950.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	ENST00000287152.12	TSL:2 MANE Select	c.1919G>T	p.Arg640Leu	missense	Exon 17 of 23	ENSP00000287152.7	Q6ZMV9-1
	KIF6	ENST00000458470.5	TSL:1	c.1592G>T	p.Arg531Leu	missense	Exon 14 of 19	ENSP00000409417.1	H0Y718
	KIF6	ENST00000229913.9	TSL:1	c.272G>T	p.Arg91Leu	missense	Exon 4 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.81
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.0011
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.19
Sift	Benign	0.033	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.36		Loss of MoRF binding (P = 0.0399)
MVP		0.56
MPC		0.10
ClinPred		0.58	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.21
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs188790180; hg19: chr6-39330237; COSMIC: COSV54694253;