6-33405423-C-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002263.4(KIFC1):c.1328C>G(p.Ser443Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,604,436 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 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
KIFC1
NM_002263.4 missense
NM_002263.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 0.521
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]
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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=0.15030485).
BS2
?
High AC in GnomAd at 48 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIFC1 | NM_002263.4 | c.1328C>G | p.Ser443Cys | missense_variant | 7/11 | ENST00000428849.7 | |
KIFC1 | XM_011514585.2 | c.1328C>G | p.Ser443Cys | missense_variant | 7/12 | ||
KIFC1 | XM_017010837.2 | c.1205C>G | p.Ser402Cys | missense_variant | 7/11 | ||
KIFC1 | XM_011514587.3 | c.757-773C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIFC1 | ENST00000428849.7 | c.1328C>G | p.Ser443Cys | missense_variant | 7/11 | 1 | NM_002263.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000111 AC: 27AN: 244168Hom.: 0 AF XY: 0.0000531 AC XY: 7AN XY: 131794
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GnomAD4 exome AF: 0.0000289 AC: 42AN: 1452086Hom.: 0 Cov.: 32 AF XY: 0.0000194 AC XY: 14AN XY: 721138
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GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152350Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74496
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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 | Nov 08, 2021 | The c.1328C>G (p.S443C) 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 1328, causing the serine (S) at amino acid position 443 to be replaced by a cysteine (C). 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
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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