chr3-47240989-A-G

Position:

• chr3-47240989-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182902.4(KIF9):​c.1736T>C​(p.Val579Ala) 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. 15/21 in silico tools predict 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: -0.0170

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026231289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF9	NM_182902.4	c.1736T>C	p.Val579Ala	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.1736T>C	p.Val579Ala	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

Sep 29, 2023

The c.1736T>C (p.V579A) 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 1736, causing the valine (V) at amino acid position 579 to be replaced by an alanine (A). 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	Benign	0.080
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.016	T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.71	T;.;T;.
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.026	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;.;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.10	N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.38	T;T;T;T
Sift4G	Benign	0.75	T;T;T;T
Polyphen		0.015	B;B;B;B
Vest4		0.077
MutPred		0.060		Gain of glycosylation at P574 (P = 0.1899);Gain of glycosylation at P574 (P = 0.1899);.;Gain of glycosylation at P574 (P = 0.1899);
MVP		0.47
MPC		0.19
ClinPred		0.044	T
GERP RS		-2.3
Varity_R		0.033
gMVP		0.33

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: chr3-47282479;