3-47240860-C-G

Variant names:

• chr3-47240860-C-G
• rs780918981
• NM_182902.4:c.1865G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182902.4(KIF9):​c.1865G>C​(p.Arg622Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R622Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF9 NM_182902.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10635027).

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.1865G>C	p.Arg622Pro	missense	Exon 17 of 21	NP_878905.2	Q9HAQ2-1
	KIF9	NM_001413976.1		c.1964G>C	p.Arg655Pro	missense	Exon 17 of 21	NP_001400905.1
	KIF9	NM_001413975.1		c.1907G>C	p.Arg636Pro	missense	Exon 18 of 22	NP_001400904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF9	ENST00000684063.1	MANE Select	c.1865G>C	p.Arg622Pro	missense	Exon 17 of 21	ENSP00000507186.1	Q9HAQ2-1
	KIF9	ENST00000452770.6	TSL:1	c.1865G>C	p.Arg622Pro	missense	Exon 18 of 22	ENSP00000391100.2	Q9HAQ2-1
	KIF9	ENST00000444589.6	TSL:1	c.1670G>C	p.Arg557Pro	missense	Exon 16 of 20	ENSP00000414987.2	Q9HAQ2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.13
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.15
Sift	Uncertain	0.020	D
Sift4G	Benign	0.21	T
Polyphen		0.44	B
Vest4		0.40
MutPred		0.29		Loss of MoRF binding (P = 0.002)
MVP		0.41
MPC		0.45
ClinPred		0.76	D
GERP RS		-6.3
Varity_R		0.53
gMVP		0.75
Mutation Taster		=81/19	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: rs780918981; hg19: chr3-47282350;