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GeneBe

X-70330248-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012310.5(KIF4A):c.987T>C(p.Tyr329=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,209,552 control chromosomes in the GnomAD database, including 1,572 homozygotes. There are 23,917 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.056 ( 154 hom., 1887 hem., cov: 22)
Exomes 𝑓: 0.056 ( 1418 hom. 22030 hem. )

Consequence

KIF4A
NM_012310.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.416
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-70330248-T-C is Benign according to our data. Variant chrX-70330248-T-C is described in ClinVar as [Benign]. Clinvar id is 1300075.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-70330248-T-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.416 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KIF4ANM_012310.5 linkuse as main transcriptc.987T>C p.Tyr329= synonymous_variant 9/31 ENST00000374403.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KIF4AENST00000374403.4 linkuse as main transcriptc.987T>C p.Tyr329= synonymous_variant 9/311 NM_012310.5 P1O95239-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0561
AC:
6275
AN:
111784
Hom.:
153
Cov.:
22
AF XY:
0.0553
AC XY:
1879
AN XY:
33962
show subpopulations
Gnomad AFR
AF:
0.0458
Gnomad AMI
AF:
0.146
Gnomad AMR
AF:
0.0820
Gnomad ASJ
AF:
0.0763
Gnomad EAS
AF:
0.141
Gnomad SAS
AF:
0.150
Gnomad FIN
AF:
0.0376
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0463
Gnomad OTH
AF:
0.0618
GnomAD3 exomes
AF:
0.0776
AC:
14205
AN:
183017
Hom.:
457
AF XY:
0.0804
AC XY:
5433
AN XY:
67611
show subpopulations
Gnomad AFR exome
AF:
0.0473
Gnomad AMR exome
AF:
0.101
Gnomad ASJ exome
AF:
0.0763
Gnomad EAS exome
AF:
0.146
Gnomad SAS exome
AF:
0.170
Gnomad FIN exome
AF:
0.0425
Gnomad NFE exome
AF:
0.0491
Gnomad OTH exome
AF:
0.0682
GnomAD4 exome
AF:
0.0565
AC:
62017
AN:
1097712
Hom.:
1418
Cov.:
30
AF XY:
0.0607
AC XY:
22030
AN XY:
363182
show subpopulations
Gnomad4 AFR exome
AF:
0.0523
Gnomad4 AMR exome
AF:
0.100
Gnomad4 ASJ exome
AF:
0.0839
Gnomad4 EAS exome
AF:
0.126
Gnomad4 SAS exome
AF:
0.163
Gnomad4 FIN exome
AF:
0.0442
Gnomad4 NFE exome
AF:
0.0450
Gnomad4 OTH exome
AF:
0.0642
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0562
AC:
6281
AN:
111840
Hom.:
154
Cov.:
22
AF XY:
0.0555
AC XY:
1887
AN XY:
34028
show subpopulations
Gnomad4 AFR
AF:
0.0460
Gnomad4 AMR
AF:
0.0817
Gnomad4 ASJ
AF:
0.0763
Gnomad4 EAS
AF:
0.140
Gnomad4 SAS
AF:
0.151
Gnomad4 FIN
AF:
0.0376
Gnomad4 NFE
AF:
0.0463
Gnomad4 OTH
AF:
0.0611
Alfa
AF:
0.0534
Hom.:
400
Bravo
AF:
0.0619

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, X-linked 100 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 19, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
8.1
Dann
Benign
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.

Other links and lift over

dbSNP: rs41305391; hg19: chrX-69550098; COSMIC: COSV65542175; API