6-33405229-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_002263.4(KIFC1):c.1134C>G(p.Phe378Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
KIFC1
NM_002263.4 missense
NM_002263.4 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 2.75
Genes affected
KIFC1 (HGNC:6389): (kinesin family member C1) Predicted to enable microtubule binding activity and minus-end-directed microtubule motor activity. Involved in mitotic metaphase plate congression and mitotic spindle assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.96
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIFC1 | NM_002263.4 | c.1134C>G | p.Phe378Leu | missense_variant | 7/11 | ENST00000428849.7 | |
KIFC1 | XM_011514585.2 | c.1134C>G | p.Phe378Leu | missense_variant | 7/12 | ||
KIFC1 | XM_017010837.2 | c.1011C>G | p.Phe337Leu | missense_variant | 7/11 | ||
KIFC1 | XM_011514587.3 | c.757-967C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIFC1 | ENST00000428849.7 | c.1134C>G | p.Phe378Leu | missense_variant | 7/11 | 1 | NM_002263.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152212
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251148Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135832
GnomAD3 exomes
AF:
AC:
4
AN:
251148
Hom.:
AF XY:
AC XY:
2
AN XY:
135832
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727238
GnomAD4 exome
AF:
AC:
52
AN:
1461864
Hom.:
Cov.:
33
AF XY:
AC XY:
22
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74346
GnomAD4 genome
?
AF:
AC:
4
AN:
152212
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Mar 29, 2023 | The c.1134C>G (p.F378L) alteration is located in exon 7 (coding exon 7) of the KIFC1 gene. This alteration results from a C to G substitution at nucleotide position 1134, causing the phenylalanine (F) at amino acid position 378 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
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at F378 (P = 0.0391);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at