chrX-70290793-G-A

Variant names:

• chrX-70290793-G-A
• NM_012310.5:c.223G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012310.5(KIF4A):​c.223G>A​(p.Gly75Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: KIF4A NM_012310.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF4A	NM_012310.5	c.223G>A	p.Gly75Ser	missense_variant	Exon 3 of 31	ENST00000374403.4	NP_036442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF4A	ENST00000374403.4	c.223G>A	p.Gly75Ser	missense_variant	Exon 3 of 31	1	NM_012310.5	ENSP00000363524.3
KIF4A	ENST00000485406.1	n.468G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 29, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.68	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.34
Sift	Benign	0.072	T
Sift4G	Benign	0.17	T
Polyphen		0.0030	B
Vest4		0.45
MutPred		0.61		Loss of catalytic residue at P71 (P = 0.0711);
MVP		0.98
MPC		1.7
ClinPred		0.95	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69510643;