NM_014679.5:c.26C>T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014679.5(CEP57):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A9T) has been classified as Likely benign.
Frequency
Consequence
NM_014679.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247894Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134618
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461734Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727162
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74402
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.A9V variant (also known as c.26C>T), located in coding exon 1 of the CEP57 gene, results from a C to T substitution at nucleotide position 26. The alanine at codon 9 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Mosaic variegated aneuploidy syndrome 2 Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 9 of the CEP57 protein (p.Ala9Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CEP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 539589). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; 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