NM_145027.6:c.1919G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF6	NM_145027.6	c.1919G>T	p.Arg640Leu	missense_variant	Exon 17 of 23	ENST00000287152.12	NP_659464.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF6	ENST00000287152.12	c.1919G>T	p.Arg640Leu	missense_variant	Exon 17 of 23	2	NM_145027.6	ENSP00000287152.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D;D;D;.
REVEL	Benign	0.19
Sift	Benign	0.033	D;T;T;.
Sift4G	Benign	0.21	T;D;D;D
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

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

LitVar

Other links and lift over

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