6-166999461-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_007045.4(CEP43):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,484,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
CEP43
NM_007045.4 missense
NM_007045.4 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 0.367
Genes affected
CEP43 (HGNC:17012): (centrosomal protein 43) This gene encodes a largely hydrophilic centrosomal protein that is required for anchoring microtubules to subcellular structures. A t(6;8)(q27;p11) chromosomal translocation, fusing this gene and the fibroblast growth factor receptor 1 (FGFR1) gene, has been found in cases of myeloproliferative disorder. The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic domain of FGFR1. Alterations in this gene may also be associated with Crohn's disease, Graves' disease, and vitiligo. Alternatively spliced transcript variants that encode different proteins have been identified. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.781
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP43 | NM_007045.4 | c.49C>T | p.Arg17Trp | missense_variant | 1/13 | ENST00000366847.9 | |
CEP43 | NM_194429.3 | c.49C>T | p.Arg17Trp | missense_variant | 1/12 | ||
CEP43 | NM_001278690.2 | c.49C>T | p.Arg17Trp | missense_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP43 | ENST00000366847.9 | c.49C>T | p.Arg17Trp | missense_variant | 1/13 | 1 | NM_007045.4 | P4 | |
ENST00000649589.1 | n.51G>A | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152216Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000995 AC: 10AN: 100506Hom.: 0 AF XY: 0.0000730 AC XY: 4AN XY: 54820
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GnomAD4 exome AF: 0.000113 AC: 150AN: 1331950Hom.: 1 Cov.: 30 AF XY: 0.0000990 AC XY: 65AN XY: 656642
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GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152216Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10AN XY: 74362
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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 | Aug 02, 2021 | The c.49C>T (p.R17W) alteration is located in exon 1 (coding exon 1) of the FGFR1OP gene. This alteration results from a C to T substitution at nucleotide position 49, causing the arginine (R) at amino acid position 17 to be replaced by a tryptophan (W). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
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