chr9-34306412-C-A

Variant names:

• chr9-34306412-C-A
• rs17350674
• NM_194313.4:c.653G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68
• Publications: 25 publications found

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)

ACMG classification

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	c.653G>T	p.Trp218Leu	missense_variant	Exon 3 of 13	ENST00000402558.7	NP_919289.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20886 AN: 152062 Hom.: 1921 Cov.: 32

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

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.: 30 AF XY: 0.177 AC XY: 128490 AN XY: 723922

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: 63 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

GnomAD4 genome AF: 0.137 AC: 20890 AN: 152180 Hom.: 1924 Cov.: 32 AF XY: 0.137 AC XY: 10158 AN XY: 74402

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: 25 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: 49 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13166 AN: 67994

Other (OTH) AF: 0.152 AC: 321 AN: 2116

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	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PhyloP100		5.7
PrimateAI	Uncertain	0.71	T
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	T
GERP RS		5.6
Varity_R		0.52
gMVP		0.37
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17350674; hg19: chr9-34306410; COSMIC: COSV61457238;