X-70290485-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_012310.5(KIF4A):c.27C>T(p.Pro9=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.752

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]

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]

ACMG classification

Verdict is Benign. Variant got -9 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_single_submitter, 1 stars. Variant chrX-70290485-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.752 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 56859 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF4A	NM_012310.5	c.27C>T	p.Pro9=	synonymous_variant	2/31	ENST00000374403.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF4A	ENST00000374403.4	c.27C>T	p.Pro9=	synonymous_variant	2/31	1	NM_012310.5	P1
PDZD11	ENST00000486461.2	c.-95G>A		5_prime_UTR_variant	1/7	3		P1
KIF4A	ENST00000485406.1	n.272C>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 109279 AN: 110134 Hom.: 38312 Cov.: 22 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

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.: 45 AF XY: 0.991 AC XY: 360040 AN XY: 363306

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.: 22 AF XY: 0.992 AC XY: 32123 AN XY: 32377

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 100 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs1199470; hg19: chrX-69510335;