rs144843732
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030928.4(CDT1):c.1631A>T(p.Glu544Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,589,160 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E544D) has been classified as Likely benign.
Frequency
Consequence
NM_030928.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDT1 | NM_030928.4 | c.1631A>T | p.Glu544Val | missense_variant | 10/10 | ENST00000301019.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDT1 | ENST00000301019.9 | c.1631A>T | p.Glu544Val | missense_variant | 10/10 | 1 | NM_030928.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00187 AC: 284AN: 152188Hom.: 1 Cov.: 35
GnomAD3 exomes AF: 0.00145 AC: 296AN: 204448Hom.: 0 AF XY: 0.00139 AC XY: 154AN XY: 110658
GnomAD4 exome AF: 0.00297 AC: 4271AN: 1436854Hom.: 14 Cov.: 34 AF XY: 0.00285 AC XY: 2034AN XY: 712668
GnomAD4 genome ? AF: 0.00186 AC: 284AN: 152306Hom.: 1 Cov.: 35 AF XY: 0.00148 AC XY: 110AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2018 | The E544V variant in the CDT1 gene has been published previously in a single individual with abnormality of growth (Retterer et al., 2016). The E544V variant is observed in 290/102030 (0.28%) alleles from individuals of non-Finnish European background in large population cohorts, and one individual is reported to be homozygous (Lek et al., 2016). The E544V variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret E544V as a variant of uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | CDT1: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 17, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at