6-17794263-G-A

Variant names:

• chr6-17794263-G-A
• rs3734234
• NM_022113.6:c.3208C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022113.6(KIF13A):​c.3208C>T​(p.Leu1070Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,609,990 control chromosomes in the GnomAD database, including 152,054 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 0.36 (11252 hom., cov: 31)
  • Exomes 𝑓: 0.44 (140802 hom.)
• Consequence: KIF13A NM_022113.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 18 publications found

Genes affected

KIF13A (HGNC:14566): (kinesin family member 13A) This gene encodes a member of the kinesin family of microtubule-based motor proteins that function in the positioning of endosomes. This family member can direct mannose-6-phosphate receptor-containing vesicles from the trans-Golgi network to the plasma membrane, and it is necessary for the steady-state distribution of late endosomes/lysosomes. It is also required for the translocation of FYVE-CENT and TTC19 from the centrosome to the midbody during cytokinesis, and it plays a role in melanosome maturation. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=3.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022113.6. 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
	KIF13A	NM_022113.6	MANE Select	c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 39	NP_071396.4
	KIF13A	NM_001105566.3		c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 38	NP_001099036.1
	KIF13A	NM_001105567.3		c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 37	NP_001099037.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF13A	ENST00000259711.11	TSL:1 MANE Select	c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 39	ENSP00000259711.6
	KIF13A	ENST00000378826.6	TSL:1	c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 38	ENSP00000368103.2
	KIF13A	ENST00000378843.6	TSL:1	c.3208C>T	p.Leu1070Leu	synonymous	Exon 25 of 37	ENSP00000368120.2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55319 AN: 151756 Hom.: 11256 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.418 AC: 104005 AN: 248690 AF XY: 0.419

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.435 AC: 634290 AN: 1458114 Hom.: 140802 Cov.: 34 AF XY: 0.433 AC XY: 314088 AN XY: 725348

African (AFR) AF: 0.167 AC: 5581 AN: 33434

American (AMR) AF: 0.421 AC: 18782 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10670 AN: 26094

East Asian (EAS) AF: 0.604 AC: 23953 AN: 39674

South Asian (SAS) AF: 0.365 AC: 31473 AN: 86154

European-Finnish (FIN) AF: 0.410 AC: 21915 AN: 53390

Middle Eastern (MID) AF: 0.391 AC: 2249 AN: 5746

European-Non Finnish (NFE) AF: 0.446 AC: 494332 AN: 1108720

Other (OTH) AF: 0.421 AC: 25335 AN: 60238

GnomAD4 genome AF: 0.364 AC: 55336 AN: 151876 Hom.: 11252 Cov.: 31 AF XY: 0.367 AC XY: 27201 AN XY: 74210

African (AFR) AF: 0.179 AC: 7406 AN: 41448

American (AMR) AF: 0.423 AC: 6452 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3044 AN: 5132

South Asian (SAS) AF: 0.377 AC: 1814 AN: 4808

European-Finnish (FIN) AF: 0.398 AC: 4193 AN: 10538

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29771 AN: 67926

Other (OTH) AF: 0.395 AC: 833 AN: 2110

Alfa AF: 0.411 Hom.: 21176

Bravo AF: 0.363

Asia WGS AF: 0.460 AC: 1600 AN: 3478

EpiCase AF: 0.422

EpiControl AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.4
DANN	Benign	0.78
PhyloP100		3.1
PromoterAI		0.00060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3734234; hg19: chr6-17794494; COSMIC: COSV52451494;