Genetic Variant NM_194313.4:c.653G>T (chr9-34306412-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194313.4(KIF24):c.653G>T(p.Trp218Leu) variant causes a missense change. The variant allele was found at a frequency of 0.174 in 1,607,156 control chromosomes in the GnomAD database, including 27,155 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 0.14 ( 1924 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25231 hom. )

Consequence

KIF24
NM_194313.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.68

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

KIF24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016726851).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF24	NM_194313.4 link	c.653G>T	p.Trp218Leu	missense_variant	Exon 3 of 13	ENST00000402558.7	NP_919289.2	Q5T7B8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF24	ENST00000402558.7 link	c.653G>T	p.Trp218Leu	missense_variant	Exon 3 of 13	5	NM_194313.4	ENSP00000384433.1		Q5T7B8-1
KIF24	ENST00000379174.7 link	c.653G>T	p.Trp218Leu	missense_variant	Exon 2 of 9	5		ENSP00000368472.3		Q5T7B8-2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20886

AN:

152062

Hom.:

1921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.00481

Gnomad SAS

AF:

0.0960

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.159

AC:

38722

AN:

244074

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.00211

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.178

AC:

258988

AN:

1454976

Hom.:

25231

Cov.:

AF XY:

0.177

AC XY:

128490

AN XY:

723922

show subpopulations

African (AFR)

AF:

0.0266

AC:

877

AN:

33024

American (AMR)

AF:

0.128

AC:

5560

AN:

43414

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6131

AN:

25966

East Asian (EAS)

AF:

0.00159

AC:

AN:

39668

South Asian (SAS)

AF:

0.109

AC:

9321

AN:

85130

European-Finnish (FIN)

AF:

0.227

AC:

12076

AN:

53294

Middle Eastern (MID)

AF:

0.165

AC:

946

AN:

5740

European-Non Finnish (NFE)

AF:

0.193

AC:

213860

AN:

1108662

Other (OTH)

AF:

0.169

AC:

10154

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9088

18176

27264

36352

45440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7238

14476

21714

28952

36190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20890

AN:

152180

Hom.:

1924

Cov.:

AF XY:

0.137

AC XY:

10158

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0336

AC:

1396

AN:

41538

American (AMR)

AF:

0.144

AC:

2197

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

835

AN:

3468

East Asian (EAS)

AF:

0.00482

AC:

AN:

5186

South Asian (SAS)

AF:

0.0955

AC:

461

AN:

4828

European-Finnish (FIN)

AF:

0.226

AC:

2389

AN:

10560

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13166

AN:

67994

Other (OTH)

AF:

0.152

AC:

321

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

915

1830

2744

3659

4574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.176

Hom.:

9981

Bravo

AF:

0.130

TwinsUK

AF:

0.190

AC:

706

ALSPAC

AF:

0.181

AC:

696

ESP6500AA

AF:

0.0332

AC:

120

ESP6500EA

AF:

0.192

AC:

1565

ExAC

AF:

0.159

AC:

19144

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L

PhyloP100

5.7

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.6

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.44

T;T

Polyphen

0.98

D;.

Vest4

0.23

ClinPred

0.041

GERP RS

5.6

Varity_R

0.52

gMVP

0.37

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over