chr22-19482803-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003504.5(CDC45):c.318C>T(p.Val106Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,980 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 (★).
Frequency
Consequence
NM_003504.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461682Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727168
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74458
ClinVar
Submissions by phenotype
Meier-Gorlin syndrome 7 Pathogenic:1
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not provided Uncertain:1
This sequence change affects codon 106 of the CDC45 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CDC45 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs745800041, gnomAD 0.01%). This variant has been observed in individual(s) with clinical features of CDC45-related conditions (PMID: 27374770). ClinVar contains an entry for this variant (Variation ID: 253098). Studies have shown that this variant results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 27374770). 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