chr3-47235541-T-C

Variant names:

• chr3-47235541-T-C
• rs753104206
• NM_182902.4:c.2294A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182902.4(KIF9):​c.2294A>G​(p.Tyr765Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF9 NM_182902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

Genes affected

KIF9 (HGNC:16666): (kinesin family member 9) Enables identical protein binding activity. Involved in extracellular matrix disassembly; organelle disassembly; and regulation of podosome assembly. Located in microtubule; podosome; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

KIF9-AS1 (HGNC:26822): (KIF9 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182902.4. 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
	KIF9	NM_182902.4	MANE Select	c.2294A>G	p.Tyr765Cys	missense	Exon 20 of 21	NP_878905.2	Q9HAQ2-1
	KIF9	NM_001413976.1		c.2393A>G	p.Tyr798Cys	missense	Exon 20 of 21	NP_001400905.1
	KIF9	NM_001413975.1		c.2336A>G	p.Tyr779Cys	missense	Exon 21 of 22	NP_001400904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF9	ENST00000684063.1	MANE Select	c.2294A>G	p.Tyr765Cys	missense	Exon 20 of 21	ENSP00000507186.1	Q9HAQ2-1
	KIF9	ENST00000452770.6	TSL:1	c.2294A>G	p.Tyr765Cys	missense	Exon 21 of 22	ENSP00000391100.2	Q9HAQ2-1
	KIF9	ENST00000444589.6	TSL:1	c.2099A>G	p.Tyr700Cys	missense	Exon 19 of 20	ENSP00000414987.2	Q9HAQ2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.98	D
Vest4		0.80
MutPred		0.59		Loss of phosphorylation at Y765 (P = 0.0484)
MVP		0.81
MPC		0.65
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.28
gMVP		0.65
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753104206; hg19: chr3-47277031;