Variant chrX-70299148-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF4A	NM_012310.5 linkuse as main transcript	c.462A>G	p.Pro154Pro	synonymous_variant	5/31	ENST00000374403.4	NP_036442.3	O95239-1Q59HG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF4A	ENST00000374403.4 linkuse as main transcript	c.462A>G	p.Pro154Pro	synonymous_variant	5/31	1	NM_012310.5	ENSP00000363524.3		O95239-1

Frequencies

GnomAD3 genomes

AF:

0.000767

AC:

AN:

112059

Hom.:

Cov.:

AF XY:

0.000789

AC XY:

AN XY:

34225

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

GnomAD3 exomes

AF:

0.000754

AC:

136

AN:

180450

Hom.:

AF XY:

0.000983

AC XY:

AN XY:

65074

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 SAS exome

AF:

0.00262

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

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00313

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.000741

GnomAD4 genome

AF:

0.000776

AC:

AN:

112112

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

AN XY:

34288

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.000284

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00189

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00196

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000888

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

KIF4A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.7

DANN

Benign

0.72

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