3-47240815-A-G

Position:

• chr3-47240815-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182902.4(KIF9):​c.1910T>C​(p.Leu637Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF9 NM_182902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28577733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF9	NM_182902.4	c.1910T>C	p.Leu637Pro	missense_variant	17/21	ENST00000684063.1	NP_878905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF9	ENST00000684063.1	c.1910T>C	p.Leu637Pro	missense_variant	17/21		NM_182902.4	ENSP00000507186.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.1910T>C (p.L637P) alteration is located in exon 18 (coding exon 16) of the KIF9 gene. This alteration results from a T to C substitution at nucleotide position 1910, causing the leucine (L) at amino acid position 637 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.033	T;T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	T;.;T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.98	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.28	T;T;T;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.72	P;P;D;P
Vest4		0.53
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);
MVP		0.79
MPC		0.40
ClinPred		0.73	D
GERP RS		4.8
Varity_R		0.50
gMVP		0.69

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: chr3-47282305;