chr3-47236044-A-G

Position:

• chr3-47236044-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182902.4(KIF9):​c.2207T>C​(p.Ile736Thr) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF9 NM_182902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17553037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF9	NM_182902.4	c.2207T>C	p.Ile736Thr	missense_variant	19/21	ENST00000684063.1	NP_878905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF9	ENST00000684063.1	c.2207T>C	p.Ile736Thr	missense_variant	19/21		NM_182902.4	ENSP00000507186.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 03, 2023

The c.2207T>C (p.I736T) alteration is located in exon 20 (coding exon 18) of the KIF9 gene. This alteration results from a T to C substitution at nucleotide position 2207, causing the isoleucine (I) at amino acid position 736 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0017
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	T;.;T;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M;M;.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.97	N;N;N;N
REVEL	Benign	0.058
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.062	B;B;B;B
Vest4		0.40
MutPred		0.38		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		0.68
MPC		0.20
ClinPred		0.34	T
GERP RS		6.1
Varity_R		0.13
gMVP		0.21

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: chr3-47277534;