chr12-94308821-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016122.3(CEP83):c.2098G>A(p.Gly700Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,606,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G700E) has been classified as Uncertain significance.
Frequency
Consequence
NM_016122.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP83 | ENST00000397809.10 | c.2098G>A | p.Gly700Arg | missense_variant | Exon 17 of 17 | 1 | NM_016122.3 | ENSP00000380911.4 | ||
CEP83 | ENST00000339839.9 | c.2098G>A | p.Gly700Arg | missense_variant | Exon 16 of 16 | 1 | ENSP00000344655.5 | |||
CEP83 | ENST00000552632.5 | c.490G>A | p.Gly164Arg | missense_variant | Exon 4 of 5 | 3 | ENSP00000447094.1 | |||
CEP83 | ENST00000546783.1 | n.*6G>A | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248600Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134876
GnomAD4 exome AF: 0.00000963 AC: 14AN: 1454492Hom.: 0 Cov.: 28 AF XY: 0.00000691 AC XY: 5AN XY: 723964
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2098G>A (p.G700R) alteration is located in exon 17 (coding exon 15) of the CEP83 gene. This alteration results from a G to A substitution at nucleotide position 2098, causing the glycine (G) at amino acid position 700 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Nephronophthisis 18 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 845600). This variant has not been reported in the literature in individuals affected with CEP83-related conditions. This variant is present in population databases (rs753799181, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 700 of the CEP83 protein (p.Gly700Arg). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at