6-39357302-A-C

Variant names:

• chr6-39357302-A-C
• rs20455
• NM_145027.6:c.2155T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145027.6(KIF6):​c.2155T>G​(p.Trp719Gly) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. W719R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF6 NM_145027.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• 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: 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=0.044843674).

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.2155T>G	p.Trp719Gly	missense	Exon 19 of 23	NP_659464.3
	KIF6	NM_001289020.3		c.2104T>G	p.Trp702Gly	missense	Exon 18 of 22	NP_001275949.1
	KIF6	NM_001289021.3		c.1987T>G	p.Trp663Gly	missense	Exon 18 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.2155T>G	p.Trp719Gly	missense	Exon 19 of 23	ENSP00000287152.7	Q6ZMV9-1
	KIF6	ENST00000458470.5	TSL:1	c.1828T>G	p.Trp610Gly	missense	Exon 16 of 19	ENSP00000409417.1	H0Y718
	KIF6	ENST00000229913.9	TSL:1	c.508T>G	p.Trp170Gly	missense	Exon 6 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
PhyloP100		0.061
Varity_R		0.044
gMVP		0.31
Mutation Taster		=96/4	polymorphism

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.

Other links and lift over

dbSNP: rs20455; hg19: chr6-39325078;