chr11-95799274-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate
The NM_014679.5(CEP57):c.88C>T(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,884 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_014679.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP57 | NM_014679.5 | c.88C>T | p.Arg30Trp | missense_variant | 2/11 | ENST00000325542.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP57 | ENST00000325542.10 | c.88C>T | p.Arg30Trp | missense_variant | 2/11 | 1 | NM_014679.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251138Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135734
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461708Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727154
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2018 | This sequence change replaces arginine with tryptophan at codon 30 of the CEP57 protein (p.Arg30Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs749693319, ExAC 0.02%). This variant has not been reported in the literature in individuals with CEP57-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at