Variant rs376405554 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_012310.5(KIF4A):c.2976+10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000884 in 1,187,347 control chromosomes in the GnomAD database, including 2 homozygotes. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00044 ( 2 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000052 ( 0 hom. 18 hem. )

Consequence

KIF4A
NM_012310.5 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.677

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-70405915-T-A is Benign according to our data. Variant chrX-70405915-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435644.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF4A	NM_012310.5 linkuse as main transcript	c.2976+10T>A		intron_variant		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.2976+10T>A		intron_variant		1	NM_012310.5	ENSP00000363524.3		O95239-1

Frequencies

GnomAD3 genomes

AF:

0.000432

AC:

AN:

110994

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33230

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00227

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00270

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

182276

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000580

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1076298

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

342798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000465

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000365

Gnomad4 OTH exome

AF:

0.000859

GnomAD4 genome

AF:

0.000441

AC:

AN:

111049

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33295

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00227

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000128

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 03, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

KIF4A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 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

-0.78

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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