9-34256467-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_194313.4(KIF24):c.3140G>T(p.Gly1047Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,613,820 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (19 hom.)
• Consequence: KIF24 NM_194313.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005818993).
• BP6: Variant 9-34256467-C-A is Benign according to our data. Variant chr9-34256467-C-A is described in ClinVar as [Benign]. Clinvar id is 791298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0077 (1172/152200) while in subpopulation AFR AF= 0.0266 (1106/41538). AF 95% confidence interval is 0.0253. There are 12 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF24	NM_194313.4	c.3140G>T	p.Gly1047Val	missense_variant	11/13	ENST00000402558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF24	ENST00000402558.7	c.3140G>T	p.Gly1047Val	missense_variant	11/13	5	NM_194313.4	P1
KIF24	ENST00000379174.7	c.2738G>T	p.Gly913Val	missense_variant	7/9	5

Frequencies

GnomAD3 genomes AF: 0.00774 AC: 1177 AN: 152082 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00209 AC: 525 AN: 250810 Hom.: 10 AF XY: 0.00144 AC XY: 195 AN XY: 135516

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000762 AC: 1114 AN: 1461620 Hom.: 19 Cov.: 36 AF XY: 0.000620 AC XY: 451 AN XY: 727092

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000450

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00770 AC: 1172 AN: 152200 Hom.: 12 Cov.: 32 AF XY: 0.00689 AC XY: 513 AN XY: 74432

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00383 Hom.: 3

Bravo AF: 0.00899

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0277 AC: 122

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00263 AC: 319

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;.
Vest4		0.38
MVP		0.89
ClinPred		0.030	T
GERP RS		3.6
Varity_R		0.35
gMVP		0.22

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

Other links and lift over

dbSNP: rs73494718; hg19: chr9-34256465;