20-32310328-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004798.4(KIF3B):​c.551C>T​(p.Thr184Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

KIF3B
NM_004798.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF3BNM_004798.4 linkuse as main transcriptc.551C>T p.Thr184Ile missense_variant 2/9 ENST00000375712.4 NP_004789.1 O15066-1
KIF3BXM_047440589.1 linkuse as main transcriptc.551C>T p.Thr184Ile missense_variant 2/9 XP_047296545.1
KIF3BXM_047440590.1 linkuse as main transcriptc.551C>T p.Thr184Ile missense_variant 2/9 XP_047296546.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF3BENST00000375712.4 linkuse as main transcriptc.551C>T p.Thr184Ile missense_variant 2/91 NM_004798.4 ENSP00000364864.3 O15066-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
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
GnomAD3 exomes
AF:
0.0000759
AC:
19
AN:
250180
Hom.:
0
AF XY:
0.0000666
AC XY:
9
AN XY:
135186
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000924
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461622
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000577
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000824
AC:
10

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 submitterclinical testingAmbry GeneticsDec 15, 2023The c.551C>T (p.T184I) alteration is located in exon 2 (coding exon 1) of the KIF3B gene. This alteration results from a C to T substitution at nucleotide position 551, causing the threonine (T) at amino acid position 184 to be replaced by an isoleucine (I). 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
0.88
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.70
D
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.50
D
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
-0.81
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.50
Sift
Benign
0.36
T
Sift4G
Benign
0.36
T
Polyphen
0.70
P
Vest4
0.77
MutPred
0.51
Loss of disorder (P = 0.045);
MVP
0.76
MPC
1.2
ClinPred
0.22
T
GERP RS
5.3
Varity_R
0.62
gMVP
0.56

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.

Other links and lift over

dbSNP: rs769441232; hg19: chr20-30898131; API