Variant 3-47244820-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182902.4(KIF9):c.1485G>C(p.Lys495Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

KIF9
NM_182902.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

KIF9 (HGNC:16666): (kinesin family member 9) Enables identical protein binding activity. Involved in extracellular matrix disassembly; organelle disassembly; and regulation of podosome assembly. Located in microtubule; podosome; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

KIF9 links:

KIF9-AS1 (HGNC:):

KIF9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1790967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF9	NM_182902.4 linkuse as main transcript	c.1485G>C	p.Lys495Asn	missense_variant	15/21	ENST00000684063.1	NP_878905.2	Q9HAQ2-1A8K932

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF9	ENST00000684063.1 linkuse as main transcript	c.1485G>C	p.Lys495Asn	missense_variant	15/21		NM_182902.4	ENSP00000507186.1		Q9HAQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251478

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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:

0.00

Alfa

AF:

0.0000359

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Apr 09, 2024

The c.1485G>C (p.K495N) alteration is located in exon 16 (coding exon 14) of the KIF9 gene. This alteration results from a G to C substitution at nucleotide position 1485, causing the lysine (K) at amino acid position 495 to be replaced by an asparagine (N). 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

0.28

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;T;.;T

Eigen

Benign

-0.040

Eigen_PC

Benign

0.0014

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

T;.;T;.

M_CAP

Benign

0.029

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.4

M;M;M;M

MutationTaster

Benign

0.71

N;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.064

Sift

Uncertain

0.017

D;D;T;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.020

B;B;P;B

Vest4

0.37

MutPred

0.28

Loss of methylation at K495 (P = 0.0022);Loss of methylation at K495 (P = 0.0022);Loss of methylation at K495 (P = 0.0022);Loss of methylation at K495 (P = 0.0022);

MVP

0.76

MPC

0.29

ClinPred

0.15

GERP RS

4.6

Varity_R

0.22

gMVP

0.27

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