rs766819113

Variant names:

• chrX-70353686-G-A
• rs766819113
• NM_012310.5:c.1553G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-70353686-G-A
• chrX-70353686-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012310.5(KIF4A):​c.1553G>A​(p.Arg518His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R518P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: KIF4A NM_012310.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10
• Publications: 1 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]

KIF4A Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 100

  Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2792095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF4A	NM_012310.5	c.1553G>A	p.Arg518His	missense_variant	Exon 15 of 31	ENST00000374403.4	NP_036442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF4A	ENST00000374403.4	c.1553G>A	p.Arg518His	missense_variant	Exon 15 of 31	1	NM_012310.5	ENSP00000363524.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000220 AC: 4 AN: 182000 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000547 AC: 6 AN: 1097389 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362761

African (AFR) AF: 0.00 AC: 0 AN: 26389

American (AMR) AF: 0.000142 AC: 5 AN: 35164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19369

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.00 AC: 0 AN: 53906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841648

Other (OTH) AF: 0.0000217 AC: 1 AN: 46081

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.27
Sift	Benign	0.13	T
Sift4G	Benign	0.087	T
Polyphen		0.14	B
Vest4		0.16
MutPred		0.34		Loss of MoRF binding (P = 0.0145);
MVP		0.88
MPC		0.45
ClinPred		0.39	T
GERP RS		4.0
Varity_R		0.21
gMVP		0.50
Mutation Taster		=85/15	polymorphism

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: rs766819113; hg19: chrX-69573536; COSMIC: COSV108222910;