dbSNP rs61748977: KIF4A:p.Pro154Pro (chrX-70299148-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012310.5(KIF4A):c.462A>G(p.Pro154Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,206,001 control chromosomes in the GnomAD database, including 2 homozygotes. There are 452 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., 27 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 2 hom. 425 hem. )

Consequence

KIF4A
NM_012310.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0370

Publications

0 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: Ambry Genetics, Illumina, G2P, 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-70299148-A-G is Benign according to our data. Variant chrX-70299148-A-G is described in ClinVar as Benign. ClinVar VariationId is 773102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.037 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 27 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.462A>G	p.Pro154Pro	synonymous	Exon 5 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.462A>G	p.Pro154Pro	synonymous	Exon 5 of 31	ENSP00000363524.3	O95239-1
KIF4A	ENST00000924316.1		c.462A>G	p.Pro154Pro	synonymous	Exon 5 of 32	ENSP00000594375.1
KIF4A	ENST00000859344.1		c.462A>G	p.Pro154Pro	synonymous	Exon 5 of 32	ENSP00000529403.1

Frequencies

GnomAD3 genomes

AF:

0.000767

AC:

AN:

112059

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00725

Gnomad AMR

AF:

0.000284

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00151

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00199

GnomAD2 exomes

AF:

0.000754

AC:

136

AN:

180450

AF XY:

0.000983

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000999

Gnomad OTH exome

AF:

0.000450

GnomAD4 exome

AF:

0.00110

AC:

1207

AN:

1093889

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

425

AN XY:

359795

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26312

American (AMR)

AF:

0.000258

AC:

AN:

34930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19262

East Asian (EAS)

AF:

0.00

AC:

AN:

30133

South Asian (SAS)

AF:

0.00313

AC:

167

AN:

53292

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40426

Middle Eastern (MID)

AF:

0.000728

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.00118

AC:

989

AN:

839503

Other (OTH)

AF:

0.000741

AC:

AN:

45910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.000776

AC:

AN:

112112

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

AN XY:

34288

show subpopulations

African (AFR)

AF:

0.000162

AC:

AN:

30932

American (AMR)

AF:

0.000284

AC:

AN:

10560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3594

South Asian (SAS)

AF:

0.00189

AC:

AN:

2639

European-Finnish (FIN)

AF:

0.000165

AC:

AN:

6075

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00122

AC:

AN:

53228

Other (OTH)

AF:

0.00196

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00102

Hom.:

Bravo

AF:

0.000888

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

KIF4A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.7

(source)

DANN

Benign

0.72

PhyloP100

-0.037

Mutation Taster

=100/0

polymorphism (auto)

(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