9-34255825-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_194313.4(KIF24):c.3782G>C(p.Arg1261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 1,613,914 control chromosomes in the GnomAD database, including 318 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 0.026 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (151 hom.)
• Consequence: KIF24 NM_194313.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.94

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=0.0020516813).
• BP6: Variant 9-34255825-C-G is Benign according to our data. Variant chr9-34255825-C-G is described in ClinVar as [Benign]. Clinvar id is 774429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF24	NM_194313.4	c.3782G>C	p.Arg1261Thr	missense_variant	11/13	ENST00000402558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF24	ENST00000402558.7	c.3782G>C	p.Arg1261Thr	missense_variant	11/13	5	NM_194313.4	P1
KIF24	ENST00000379174.7	c.3380G>C	p.Arg1127Thr	missense_variant	7/9	5

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3992 AN: 152126 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00736 AC: 1848 AN: 250992 Hom.: 60 AF XY: 0.00537 AC XY: 729 AN XY: 135656

Gnomad AFR exome AF: 0.0864

Gnomad AMR exome AF: 0.00764

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000917

Gnomad OTH exome AF: 0.00718

GnomAD4 exome AF: 0.00309 AC: 4511 AN: 1461670 Hom.: 151 Cov.: 32 AF XY: 0.00269 AC XY: 1954 AN XY: 727118

Gnomad4 AFR exome AF: 0.0864

Gnomad4 AMR exome AF: 0.00834

Gnomad4 ASJ exome AF: 0.00275

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000533

Gnomad4 OTH exome AF: 0.00841

GnomAD4 genome AF: 0.0262 AC: 3990 AN: 152244 Hom.: 167 Cov.: 32 AF XY: 0.0258 AC XY: 1918 AN XY: 74442

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00476 Hom.: 22

Bravo AF: 0.0299

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0847 AC: 373

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00857 AC: 1041

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00154

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.77	T;T
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.79	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.054	T;D
Polyphen		0.48	P;.
Vest4		0.33
MVP		0.83
ClinPred		0.033	T
GERP RS		4.6
Varity_R		0.18
gMVP		0.24

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: rs76716576; hg19: chr9-34255823;