chrX-70290485-C-T

Variant names:

• chrX-70290485-C-T
• rs1199470
• NM_012310.5:c.27C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.752
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1300073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.752 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012310.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF4A	NM_012310.5	MANE Select	c.27C>T	p.Pro9Pro	synonymous	Exon 2 of 31	NP_036442.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF4A	ENST00000374403.4	TSL:1 MANE Select	c.27C>T	p.Pro9Pro	synonymous	Exon 2 of 31	ENSP00000363524.3	O95239-1
	KIF4A	ENST00000924316.1		c.27C>T	p.Pro9Pro	synonymous	Exon 2 of 32	ENSP00000594375.1
	KIF4A	ENST00000859344.1		c.27C>T	p.Pro9Pro	synonymous	Exon 2 of 32	ENSP00000529403.1

Frequencies

GnomAD3 genomes AF: 0.992 AC: 109279 AN: 110134 Hom.: 38312 Cov.: 22

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

GnomAD2 exomes AF: 0.992 AC: 181399 AN: 182803 AF XY: 0.993

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 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

African (AFR) AF: 0.998 AC: 26356 AN: 26396

American (AMR) AF: 0.993 AC: 34953 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 18753 AN: 19368

East Asian (EAS) AF: 1.00 AC: 30204 AN: 30205

South Asian (SAS) AF: 0.998 AC: 54005 AN: 54104

European-Finnish (FIN) AF: 0.999 AC: 40473 AN: 40522

Middle Eastern (MID) AF: 0.984 AC: 3988 AN: 4053

European-Non Finnish (NFE) AF: 0.990 AC: 833275 AN: 842021

Other (OTH) AF: 0.991 AC: 45658 AN: 46068

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

African (AFR) AF: 0.999 AC: 30207 AN: 30251

American (AMR) AF: 0.987 AC: 10270 AN: 10405

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 2543 AN: 2625

East Asian (EAS) AF: 1.00 AC: 3454 AN: 3455

South Asian (SAS) AF: 0.998 AC: 2502 AN: 2507

European-Finnish (FIN) AF: 0.999 AC: 5795 AN: 5803

Middle Eastern (MID) AF: 0.977 AC: 210 AN: 215

European-Non Finnish (NFE) AF: 0.989 AC: 52191 AN: 52746

Other (OTH) AF: 0.987 AC: 1488 AN: 1507

Alfa AF: 0.989 Hom.: 16810

Bravo AF: 0.991

EpiCase AF: 0.986

EpiControl AF: 0.988

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, X-linked 100 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		-0.75
PromoterAI		-0.059	Neutral
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1199470; hg19: chrX-69510335; COSMIC: COSV108051528; COSMIC: COSV108051528;