6-39362404-C-T

Position:

• chr6-39362404-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145027.6(KIF6):​c.1946+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,565,426 control chromosomes in the GnomAD database, including 15,915 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 0.17 (2564 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13351 hom.)
• Consequence: KIF6 NM_145027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF6	NM_145027.6	c.1946+30G>A		intron_variant		ENST00000287152.12	NP_659464.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF6	ENST00000287152.12	c.1946+30G>A		intron_variant		2	NM_145027.6	ENSP00000287152.7

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25750 AN: 151780 Hom.: 2563 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.131 AC: 32822 AN: 251198 Hom.: 2419 AF XY: 0.128 AC XY: 17421 AN XY: 135756

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0461

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.133 AC: 187981 AN: 1413528 Hom.: 13351 Cov.: 25 AF XY: 0.132 AC XY: 93472 AN XY: 706024

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0436

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.170 AC: 25775 AN: 151898 Hom.: 2564 Cov.: 32 AF XY: 0.167 AC XY: 12419 AN XY: 74198

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0491

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.184

Alfa AF: 0.158 Hom.: 508

Bravo AF: 0.176

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs45460596; hg19: chr6-39330180; COSMIC: COSV54680477;