NM_012310.5:c.106C>T

Variant names:

• chrX-70290564-C-T
• NM_012310.5:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012310.5(KIF4A):​c.106C>T​(p.Pro36Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: KIF4A NM_012310.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.106C>T	p.Pro36Ser	missense	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.106C>T	p.Pro36Ser	missense	Exon 2 of 31	ENSP00000363524.3	O95239-1
	KIF4A	ENST00000924316.1		c.106C>T	p.Pro36Ser	missense	Exon 2 of 32	ENSP00000594375.1
	KIF4A	ENST00000859344.1		c.106C>T	p.Pro36Ser	missense	Exon 2 of 32	ENSP00000529403.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Benign	0.25	T
Sift4G	Benign	0.52	T
Polyphen		0.78	P
Vest4		0.32
MutPred		0.31		Gain of glycosylation at P36 (P = 0.0621)
MVP		0.79
MPC		2.3
ClinPred		0.95	D
GERP RS		6.2
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.78
Mutation Taster		=41/59	disease causing

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

hg19: chrX-69510414;