Variant 9-34256267-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194313.4(KIF24):c.3340C>G(p.Leu1114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,608,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

KIF24
NM_194313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

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]

KIF24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20606866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF24	NM_194313.4 linkuse as main transcript	c.3340C>G	p.Leu1114Val	missense_variant	11/13	ENST00000402558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF24	ENST00000402558.7 linkuse as main transcript	c.3340C>G	p.Leu1114Val	missense_variant	11/13	5	NM_194313.4	P1	Q5T7B8-1
KIF24	ENST00000379174.7 linkuse as main transcript	c.2938C>G	p.Leu980Val	missense_variant	7/9	5			Q5T7B8-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243050

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000481

AC:

AN:

1456166

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

723866

show subpopulations

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:

0.0000604

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.3340C>G (p.L1114V) alteration is located in exon 11 (coding exon 10) of the KIF24 gene. This alteration results from a C to G substitution at nucleotide position 3340, causing the leucine (L) at amino acid position 1114 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.070

T;.

Eigen

Benign

0.014

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.056

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

0.95

P;.

Vest4

0.22

MutPred

0.14

Gain of glycosylation at S1115 (P = 0.085);.;

MVP

0.84

ClinPred

0.79

GERP RS

2.1

Varity_R

0.18

gMVP

0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over