6-17764765-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022113.6(KIF13A):c.4763G>A(p.Arg1588His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
KIF13A
NM_022113.6 missense
NM_022113.6 missense
Scores
4
3
12
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
KIF13A (HGNC:14566): (kinesin family member 13A) This gene encodes a member of the kinesin family of microtubule-based motor proteins that function in the positioning of endosomes. This family member can direct mannose-6-phosphate receptor-containing vesicles from the trans-Golgi network to the plasma membrane, and it is necessary for the steady-state distribution of late endosomes/lysosomes. It is also required for the translocation of FYVE-CENT and TTC19 from the centrosome to the midbody during cytokinesis, and it plays a role in melanosome maturation. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
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=0.21896988).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF13A | NM_022113.6 | c.4763G>A | p.Arg1588His | missense_variant | 39/39 | ENST00000259711.11 | NP_071396.4 | |
KIF13A | NM_001105566.3 | c.4658G>A | p.Arg1553His | missense_variant | 38/38 | NP_001099036.1 | ||
KIF13A | NM_001105567.3 | c.4619G>A | p.Arg1540His | missense_variant | 37/37 | NP_001099037.1 | ||
KIF13A | NM_001105568.4 | c.4619G>A | p.Arg1540His | missense_variant | 37/38 | NP_001099038.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF13A | ENST00000259711.11 | c.4763G>A | p.Arg1588His | missense_variant | 39/39 | 1 | NM_022113.6 | ENSP00000259711.6 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000445 AC: 11AN: 246966Hom.: 0 AF XY: 0.0000448 AC XY: 6AN XY: 133966
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GnomAD4 exome AF: 0.0000746 AC: 109AN: 1460776Hom.: 0 Cov.: 34 AF XY: 0.0000661 AC XY: 48AN XY: 726582
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74388
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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 02, 2022 | The c.4763G>A (p.R1588H) alteration is located in exon 39 (coding exon 39) of the KIF13A gene. This alteration results from a G to A substitution at nucleotide position 4763, causing the arginine (R) at amino acid position 1588 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;T;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Benign
Sift
Benign
T;D;D;D;D;.
Sift4G
Benign
T;T;T;T;T;.
Polyphen
D;.;D;D;D;.
Vest4
MVP
MPC
0.92
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