Variant 9-34254498-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194313.4(KIF24):c.3989A>G(p.Gln1330Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

KIF24
NM_194313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015736878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF24	NM_194313.4 linkuse as main transcript	c.3989A>G	p.Gln1330Arg	missense_variant	13/13	ENST00000402558.7	NP_919289.2	Q5T7B8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF24	ENST00000402558.7 linkuse as main transcript	c.3989A>G	p.Gln1330Arg	missense_variant	13/13	5	NM_194313.4	ENSP00000384433.1		Q5T7B8-1
KIF24	ENST00000379174.7 linkuse as main transcript	c.3587A>G	p.Gln1196Arg	missense_variant	9/9	5		ENSP00000368472.3		Q5T7B8-2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000124

AC:

AN:

250700

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1461478

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000473

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00168

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:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000999

Hom.:

Bravo

AF:

0.000559

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

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

Jun 17, 2024

The c.3989A>G (p.Q1330R) alteration is located in exon 13 (coding exon 12) of the KIF24 gene. This alteration results from a A to G substitution at nucleotide position 3989, causing the glutamine (Q) at amino acid position 1330 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

0.085

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.093

Sift

Benign

0.047

D;D

Sift4G

Benign

0.37

T;T

Polyphen

0.037

B;.

Vest4

0.19

MVP

0.76

ClinPred

0.032

GERP RS

3.2

Varity_R

0.096

gMVP

0.20

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

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