2-25980432-T-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000264712.8(KIF3C):āc.1486A>Cā(p.Met496Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
KIF3C
ENST00000264712.8 missense
ENST00000264712.8 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 4.79
Genes affected
KIF3C (HGNC:6321): (kinesin family member 3C) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Predicted to act upstream of or within organelle transport along microtubule. Predicted to be located in microtubule cytoskeleton; neuronal cell body; and neuronal ribonucleoprotein granule. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07315904).
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF3C | NM_002254.8 | c.1486A>C | p.Met496Leu | missense_variant | 1/8 | ENST00000264712.8 | NP_002245.4 | |
KIF3C | XM_005264299.4 | c.1486A>C | p.Met496Leu | missense_variant | 1/8 | XP_005264356.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF3C | ENST00000264712.8 | c.1486A>C | p.Met496Leu | missense_variant | 1/8 | 1 | NM_002254.8 | ENSP00000264712.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251424Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135890
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727226
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
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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 | Jun 27, 2022 | The c.1486A>C (p.M496L) alteration is located in exon 1 (coding exon 1) of the KIF3C gene. This alteration results from a A to C substitution at nucleotide position 1486, causing the methionine (M) at amino acid position 496 to be replaced by a leucine (L). 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
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.2629);Gain of relative solvent accessibility (P = 0.2629);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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