dbSNP rs764648571: KIF4A:p.Lys224Gln (chrX-70302053-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_012310.5(KIF4A):c.670A>C(p.Lys224Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000422 in 1,209,421 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000043 ( 0 hom. 12 hem. )

Consequence

KIF4A
NM_012310.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.51

Publications

1 publications found

Variant links:

Genes affected

KIF4A (HGNC:13339): (kinesin family member 4A) This gene encodes a member of the kinesin 4 subfamily of kinesin related proteins. The encoded protein is an ATP dependent microtubule-based motor protein that is involved in the intracellular transport of membranous organelles. This protein also associates with condensed chromosome arms and may be involved in maintaining chromosome integrity during mitosis. This protein may also be involved in the organization of the central spindle prior to cytokinesis. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, Mar 2010]

KIF4A Gene-Disease associations (from GenCC):

intellectual disability, X-linked 100
Inheritance: XL, Unknown Classification: MODERATE, LIMITED Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder with or without congenital anomalies
Inheritance: XL Classification: LIMITED Submitted by: ClinGen

KIF4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26861358).

BS2

High Hemizygotes in GnomAdExome4 at 12 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012310.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF4A	NM_012310.5	MANE Select	c.670A>C	p.Lys224Gln	missense	Exon 6 of 31	NP_036442.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF4A	ENST00000374403.4	TSL:1 MANE Select	c.670A>C	p.Lys224Gln	missense	Exon 6 of 31	ENSP00000363524.3	O95239-1
KIF4A	ENST00000924316.1		c.670A>C	p.Lys224Gln	missense	Exon 6 of 32	ENSP00000594375.1
KIF4A	ENST00000859344.1		c.670A>C	p.Lys224Gln	missense	Exon 6 of 32	ENSP00000529403.1

Frequencies

GnomAD3 genomes

AF:

0.0000356

AC:

AN:

112392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000276

AC:

AN:

181140

AF XY:

0.0000304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000428

AC:

AN:

1097029

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362455

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26370

American (AMR)

AF:

0.00

AC:

AN:

35021

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19334

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

53779

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.0000558

AC:

AN:

841624

Other (OTH)

AF:

0.00

AC:

AN:

46049

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000356

AC:

AN:

112392

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30910

American (AMR)

AF:

0.00

AC:

AN:

10614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3600

South Asian (SAS)

AF:

0.00

AC:

AN:

2716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6149

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000750

AC:

AN:

53309

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.45

PhyloP100

5.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.1

REVEL

Benign

0.26

Sift

Benign

0.13

Sift4G

Benign

0.24

Polyphen

0.44

Vest4

0.23

MutPred

0.35

Loss of sheet (P = 0.0104)

MVP

0.92

MPC

2.2

ClinPred

0.25

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.55

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over