22-19480009-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003504.5(CDC45):āc.41T>Cā(p.Val14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,646 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 (ā ā ).
Frequency
Consequence
NM_003504.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152020Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250562Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135716
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461626Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727138
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152020Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.41T>C (p.V14A) alteration is located in exon 1 (coding exon 1) of the CDC45 gene. This alteration results from a T to C substitution at nucleotide position 41, causing the valine (V) at amino acid position 14 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This variant is present in population databases (rs141041145, ExAC 0.002%). This sequence change replaces valine with alanine at codon 14 of the CDC45 protein (p.Val14Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant has not been reported in the literature in individuals with CDC45-related conditions. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at