6-39339256-A-C

Variant names:

• chr6-39339256-A-C
• rs9471075
• NM_145027.6:c.2429-2708T>G

Variant summary

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

The NM_145027.6(KIF6):​c.2429-2708T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,106 control chromosomes in the GnomAD database, including 3,409 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 0.13 (3409 hom., cov: 32)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	NM_145027.6	MANE Select	c.2429-2708T>G		intron	N/A	NP_659464.3
	KIF6	NM_001289020.3		c.2378-2708T>G		intron	N/A	NP_001275949.1
	KIF6	NM_001289021.3		c.2261-2708T>G		intron	N/A	NP_001275950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	ENST00000287152.12	TSL:2 MANE Select	c.2429-2708T>G		intron	N/A	ENSP00000287152.7
	KIF6	ENST00000458470.5	TSL:1	c.2051-2708T>G		intron	N/A	ENSP00000409417.1
	KIF6	ENST00000229913.9	TSL:1	c.782-2708T>G		intron	N/A	ENSP00000229913.5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20190 AN: 151986 Hom.: 3391 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.133 AC: 20253 AN: 152106 Hom.: 3409 Cov.: 32 AF XY: 0.129 AC XY: 9626 AN XY: 74362

African (AFR) AF: 0.396 AC: 16403 AN: 41406

American (AMR) AF: 0.0692 AC: 1058 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4830

European-Finnish (FIN) AF: 0.0350 AC: 371 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1939 AN: 68000

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.0622 Hom.: 713

Bravo AF: 0.150

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.52
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs9471075; hg19: chr6-39307032;