9-34255163-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194313.4(KIF24):c.3875A>G(p.Gln1292Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,415,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KIF24 NM_194313.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30337065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF24	NM_194313.4	c.3875A>G	p.Gln1292Arg	missense_variant, splice_region_variant	12/13	ENST00000402558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF24	ENST00000402558.7	c.3875A>G	p.Gln1292Arg	missense_variant, splice_region_variant	12/13	5	NM_194313.4	P1
KIF24	ENST00000379174.7	c.3473A>G	p.Gln1158Arg	missense_variant, splice_region_variant	8/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1415394 Hom.: 0 Cov.: 28 AF XY: 0.00000428 AC XY: 3 AN XY: 701092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.0000340

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.3875A>G (p.Q1292R) alteration is located in exon 12 (coding exon 11) of the KIF24 gene. This alteration results from a A to G substitution at nucleotide position 3875, causing the glutamine (Q) at amino acid position 1292 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.98	D;.
Vest4		0.31
MutPred		0.47		Gain of MoRF binding (P = 0.0221);.;
MVP		0.90
ClinPred		0.91	D
GERP RS		3.0
Varity_R		0.20
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34255161;