16-88804003-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_030928.4(CDT1):āc.172G>Cā(p.Gly58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,454,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_030928.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDT1 | NM_030928.4 | c.172G>C | p.Gly58Arg | missense_variant | 1/10 | ENST00000301019.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDT1 | ENST00000301019.9 | c.172G>C | p.Gly58Arg | missense_variant | 1/10 | 1 | NM_030928.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000659 AC: 10AN: 151844Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000136 AC: 10AN: 73442Hom.: 0 AF XY: 0.000140 AC XY: 6AN XY: 42766
GnomAD4 exome AF: 0.0000353 AC: 46AN: 1302562Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 23AN XY: 642490
GnomAD4 genome AF: 0.0000658 AC: 10AN: 151950Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 58 of the CDT1 protein (p.Gly58Arg). This variant is present in population databases (rs767926757, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CDT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 434670). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 27, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 18, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | The c.172G>C (p.G58R) alteration is located in exon 1 (coding exon 1) of the CDT1 gene. This alteration results from a G to C substitution at nucleotide position 172, causing the glycine (G) at amino acid position 58 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at