Variant 3-47243121-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182902.4(KIF9):c.1639C>T(p.Arg547Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,686 control chromosomes in the GnomAD database, including 1 homozygotes. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

KIF9
NM_182902.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF9	NM_182902.4 linkuse as main transcript	c.1639C>T	p.Arg547Trp	missense_variant	16/21	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.1639C>T	p.Arg547Trp	missense_variant	16/21		NM_182902.4	ENSP00000507186.1		Q9HAQ2-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000235

AC:

AN:

251458

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000302

AC:

441

AN:

1461560

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

229

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000322

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000764

EpiControl

AF:

0.000237

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

May 30, 2022

The c.1639C>T (p.R547W) alteration is located in exon 17 (coding exon 15) of the KIF9 gene. This alteration results from a C to T substitution at nucleotide position 1639, causing the arginine (R) at amino acid position 547 to be replaced by a tryptophan (W). 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

0.082

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T;T

Eigen

Benign

0.044

Eigen_PC

Benign

0.00083

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.88

D;.;.

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.59

MVP

0.79

MPC

0.57

ClinPred

0.12

GERP RS

4.8

Varity_R

0.075

gMVP

0.45

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