rs371582975
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_025114.4(CEP290):c.4938A>G(p.Lys1646=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000999 in 1,541,710 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
CEP290
NM_025114.4 synonymous
NM_025114.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.62
Genes affected
CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 12-88083105-T-C is Benign according to our data. Variant chr12-88083105-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 241585.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.4938A>G | p.Lys1646= | synonymous_variant | 37/54 | ENST00000552810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.4938A>G | p.Lys1646= | synonymous_variant | 37/54 | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000648 AC: 10AN: 154422Hom.: 0 AF XY: 0.0000368 AC XY: 3AN XY: 81426
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GnomAD4 exome AF: 0.000100 AC: 139AN: 1389472Hom.: 0 Cov.: 28 AF XY: 0.0000875 AC XY: 60AN XY: 685334
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
CEP290-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2024 | The CEP290 c.4938A>G variant is not predicted to result in an amino acid change (p.=). Available splicing prediction programs indicate that this variant may lead to the creation of a novel splice donor site (Alamut Visual Plus v1.6.1). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Leber congenital amaurosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Senior-Loken syndrome 6;C1857780:Joubert syndrome 5;C1857821:Leber congenital amaurosis 10;C1970161:Meckel syndrome, type 4;C2673874:Bardet-Biedl syndrome 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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SpliceAI score (max)
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DS_DG_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at