Variant 20-32310297-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_004798.4(KIF3B):c.520G>T(p.Val174Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF3B
NM_004798.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

Variant links:

Genes affected

KIF3B (HGNC:6320): (kinesin family member 3B) The protein encoded by this gene acts as a heterodimer with kinesin family member 3A to aid in chromosome movement during mitosis and meiosis. The encoded protein is a plus end-directed microtubule motor and can interact with the SMC3 subunit of the cohesin complex. In addition, the encoded protein may be involved in the intracellular movement of membranous organelles. This protein and kinesin family member 3A form the kinesin II subfamily of the kinesin superfamily. [provided by RefSeq, Jul 2008]

KIF3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF3B. . Gene score misZ 2.9986 (greater than the threshold 3.09). Trascript score misZ 3.7442 (greater than threshold 3.09). GenCC has associacion of gene with ciliopathy, retinitis pigmentosa 89.

BP4

Computational evidence support a benign effect (MetaRNN=0.40265447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3B	NM_004798.4 linkuse as main transcript	c.520G>T	p.Val174Leu	missense_variant	2/9	ENST00000375712.4	NP_004789.1	O15066-1
KIF3B	XM_047440589.1 linkuse as main transcript	c.520G>T	p.Val174Leu	missense_variant	2/9		XP_047296545.1
KIF3B	XM_047440590.1 linkuse as main transcript	c.520G>T	p.Val174Leu	missense_variant	2/9		XP_047296546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3B	ENST00000375712.4 linkuse as main transcript	c.520G>T	p.Val174Leu	missense_variant	2/9	1	NM_004798.4	ENSP00000364864.3		O15066-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.520G>T (p.V174L) alteration is located in exon 2 (coding exon 1) of the KIF3B gene. This alteration results from a G to T substitution at nucleotide position 520, causing the valine (V) at amino acid position 174 to be replaced by a leucine (L). 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

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.035

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.52

Sift

Uncertain

0.016

Sift4G

Uncertain

0.0060

Polyphen

0.048

Vest4

0.15

MutPred

0.69

Loss of methylation at K177 (P = 0.114);

MVP

0.76

MPC

0.65

ClinPred

0.94

GERP RS

4.3

Varity_R

0.54

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over