20-32310328-C-T
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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
NM_004798.4 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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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 |
---|---|---|---|---|---|---|---|---|
KIF3B | NM_004798.4 | c.551C>T | p.Thr184Ile | missense_variant | 2/9 | ENST00000375712.4 | NP_004789.1 | |
KIF3B | XM_047440589.1 | c.551C>T | p.Thr184Ile | missense_variant | 2/9 | XP_047296545.1 | ||
KIF3B | XM_047440590.1 | c.551C>T | p.Thr184Ile | missense_variant | 2/9 | XP_047296546.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF3B | ENST00000375712.4 | c.551C>T | p.Thr184Ile | missense_variant | 2/9 | 1 | NM_004798.4 | ENSP00000364864.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000759 AC: 19AN: 250180Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135186
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461622Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727100
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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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 | Dec 15, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.045);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at