6-39339738-T-G

Variant names:

• chr6-39339738-T-G
• rs3818308
• NM_145027.6:c.2429-3190A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145027.6(KIF6):​c.2429-3190A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,966 control chromosomes in the GnomAD database, including 14,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (14194 hom., cov: 33)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 4 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]

LOC105375047 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

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.2429-3190A>C		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.2378-3190A>C		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.2261-3190A>C		intron	N/A	NP_001275950.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	ENST00000287152.12	TSL:2 MANE Select	c.2429-3190A>C		intron	N/A	ENSP00000287152.7	Q6ZMV9-1
	KIF6	ENST00000458470.5	TSL:1	c.2051-3190A>C		intron	N/A	ENSP00000409417.1	H0Y718
	KIF6	ENST00000229913.9	TSL:1	c.782-3190A>C		intron	N/A	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61057 AN: 151848 Hom.: 14162 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61145 AN: 151966 Hom.: 14194 Cov.: 33 AF XY: 0.400 AC XY: 29678 AN XY: 74260

African (AFR) AF: 0.644 AC: 26733 AN: 41484

American (AMR) AF: 0.306 AC: 4679 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3468

East Asian (EAS) AF: 0.469 AC: 2420 AN: 5158

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4808

European-Finnish (FIN) AF: 0.339 AC: 3580 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20222 AN: 67884

Other (OTH) AF: 0.372 AC: 787 AN: 2114

Alfa AF: 0.321 Hom.: 4347

Bravo AF: 0.411

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.49
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3818308; hg19: chr6-39307514;