9-34256349-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_194313.4(KIF24):c.3258G>A(p.Gly1086=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,194 control chromosomes in the GnomAD database, including 108,833 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 0.35 (9871 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98962 hom.)
• Consequence: KIF24 NM_194313.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

Genes affected

KIF24 (HGNC:19916): (kinesin family member 24) This gene encodes a member of the kinesin superfamily of microtubule-based motor proteins which are involved in the intracellular transport of membranous organelles, protein complexes, and mRNAs. They also play critical roles in mitosis, morphogenesis, and signal transduction. The encoded protein contains an N-terminal sterile alpha motif (SAM) domain and an ATP-binding kinesin motor domain. It binds centriolar coiled coil protein 110 and centrosomal protein 97 and localizes to the mother centriole to regulate ciliogenesis by controlling microtubule polymerization. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF24	NM_194313.4	c.3258G>A	p.Gly1086=	synonymous_variant	11/13	ENST00000402558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF24	ENST00000402558.7	c.3258G>A	p.Gly1086=	synonymous_variant	11/13	5	NM_194313.4	P1
KIF24	ENST00000379174.7	c.2856G>A	p.Gly952=	synonymous_variant	7/9	5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52554 AN: 151874 Hom.: 9857 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.366

GnomAD3 exomes AF: 0.404 AC: 99788 AN: 246818 Hom.: 21937 AF XY: 0.405 AC XY: 54032 AN XY: 133506

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.740

Gnomad SAS exome AF: 0.502

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.359 AC: 524177 AN: 1461202 Hom.: 98962 Cov.: 52 AF XY: 0.362 AC XY: 263189 AN XY: 726844

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.346 AC: 52602 AN: 151992 Hom.: 9871 Cov.: 32 AF XY: 0.354 AC XY: 26327 AN XY: 74302

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.371

Alfa AF: 0.340 Hom.: 14900

Bravo AF: 0.347

Asia WGS AF: 0.589 AC: 2042 AN: 3478

EpiCase AF: 0.339

EpiControl AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.47
Dann	Benign	0.53

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: rs10814083; hg19: chr9-34256347; COSMIC: COSV52658964; COSMIC: COSV52658964;