chr16-57761050-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001130100.2(KIFC3):c.1994G>A(p.Arg665His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,609,640 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
KIFC3
NM_001130100.2 missense
NM_001130100.2 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 3.35
Genes affected
KIFC3 (HGNC:6326): (kinesin family member C3) This gene encodes a member of the kinesin-14 family of microtubule motors. Members of this family play a role in the formation, maintenance and remodeling of the bipolar mitotic spindle. The protein encoded by this gene has cytoplasmic functions in the interphase cells. It may also be involved in the final stages of cytokinesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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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=0.23335552).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIFC3 | NM_001130100.2 | c.1994G>A | p.Arg665His | missense_variant | 15/20 | ENST00000445690.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIFC3 | ENST00000445690.7 | c.1994G>A | p.Arg665His | missense_variant | 15/20 | 1 | NM_001130100.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247524Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134176
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457462Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9AN XY: 724674
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN 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 | May 09, 2023 | The c.1994G>A (p.R665H) alteration is located in exon 15 (coding exon 14) of the KIFC3 gene. This alteration results from a G to A substitution at nucleotide position 1994, causing the arginine (R) at amino acid position 665 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
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
.;D;D;.;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
0.58, 0.070, 0.24
.;P;.;.;.;B;B;.;.
Vest4
MutPred
0.48
.;.;.;.;Loss of MoRF binding (P = 0.0591);.;.;.;.;
MVP
MPC
0.69
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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