rs2299006

Positions:

• chr5-132709046-C-G
• chr5-132709046-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001300791.2(KIF3A):​c.1229-68G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,206,280 control chromosomes in the GnomAD database, including 39,854 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 0.32 (10971 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28883 hom.)
• Consequence: KIF3A NM_001300791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

Genes affected

KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230612 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3A	NM_001300791.2	c.1229-68G>C		intron_variant		ENST00000403231.6	NP_001287720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3A	ENST00000403231.6	c.1229-68G>C		intron_variant		2	NM_001300791.2	ENSP00000385808.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48769 AN: 151840 Hom.: 10941 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.187 AC: 197640 AN: 1054322 Hom.: 28883 AF XY: 0.184 AC XY: 98114 AN XY: 533398

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.322 AC: 48857 AN: 151958 Hom.: 10971 Cov.: 32 AF XY: 0.331 AC XY: 24553 AN XY: 74276

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.260

Alfa AF: 0.138 Hom.: 293

Bravo AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.72

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: rs2299006; hg19: chr5-132044738;