Genetic Variant NM_012310.5:c.27C>T (chrX-70290485-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_012310.5(KIF4A):c.27C>T(p.Pro9Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 38308 hom., 32123 hem., cov: 22)

Exomes 𝑓: 0.99 ( 360351 hom. 360040 hem. )

Failed GnomAD Quality Control

Consequence

KIF4A
NM_012310.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.752

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:

PDZD11 (HGNC:28034): (PDZ domain containing 11) Enables protein C-terminus binding activity. Involved in pore complex assembly. Located in basolateral plasma membrane and cytosol. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PDZD11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-70290485-C-T is Benign according to our data. Variant chrX-70290485-C-T is described in ClinVar as [Benign]. Clinvar id is 1300073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-70290485-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.752 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF4A	NM_012310.5 link	c.27C>T	p.Pro9Pro	synonymous_variant	Exon 2 of 31	ENST00000374403.4	NP_036442.3	O95239-1Q59HG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF4A	ENST00000374403.4 link	c.27C>T	p.Pro9Pro	synonymous_variant	Exon 2 of 31	1	NM_012310.5	ENSP00000363524.3	O95239-1
PDZD11	ENST00000486461.2 link	c.-95G>A		5_prime_UTR_variant	Exon 1 of 7	3		ENSP00000512019.1	Q5EBL8-1
KIF4A	ENST00000485406.1 link	n.272C>T		non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

109279

AN:

110134

Hom.:

38312

Cov.:

AF XY:

0.992

AC XY:

32060

AN XY:

32314

FAILED QC

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.987

GnomAD3 exomes

AF:

0.992

AC:

181399

AN:

182803

Hom.:

56859

AF XY:

0.993

AC XY:

66769

AN XY:

67249

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.988

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.991

AC:

1087665

AN:

1097926

Hom.:

360351

Cov.:

AF XY:

0.991

AC XY:

360040

AN XY:

363306

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.993

Gnomad4 ASJ exome

AF:

0.968

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.990

Gnomad4 OTH exome

AF:

0.991

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.992

AC:

109333

AN:

110187

Hom.:

38308

Cov.:

AF XY:

0.992

AC XY:

32123

AN XY:

32377

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

0.987

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.998

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.989

Gnomad4 OTH

AF:

0.987

Alfa

AF:

0.989

Hom.:

16810

Bravo

AF:

0.991

EpiCase

AF:

0.986

EpiControl

AF:

0.988

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Intellectual disability, X-linked 100

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.90

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