chr5-123346554-T-C
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_001375405.1(CEP120):c.2926A>G(p.Arg976Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,264 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001375405.1 missense
Scores
Clinical Significance
Conservation
Publications
- ciliopathyInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- Joubert syndrome 31Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- short-rib thoracic dysplasia 13 with or without polydactylyInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Jeune syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Joubert syndrome with ocular defectInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP120 | NM_001375405.1 | c.2926A>G | p.Arg976Gly | missense_variant | Exon 20 of 20 | ENST00000306467.10 | NP_001362334.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152230Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000799 AC: 20AN: 250348 AF XY: 0.0000517 show subpopulations
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460916Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726738 show subpopulations
GnomAD4 genome AF: 0.000217 AC: 33AN: 152348Hom.: 1 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74498 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Short-rib thoracic dysplasia 13 with or without polydactyly 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1678836). This variant has not been reported in the literature in individuals affected with CEP120-related conditions. This variant is present in population databases (rs145436175, gnomAD 0.1%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 976 of the CEP120 protein (p.Arg976Gly). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at