rs200672589
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030928.4(CDT1):c.1357C>T(p.Arg453Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,612,572 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00040 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00071 ( 16 hom. )
Consequence
CDT1
NM_030928.4 missense
NM_030928.4 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 3.14
Genes affected
CDT1 (HGNC:24576): (chromatin licensing and DNA replication factor 1) The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.044795364).
BP6
?
Variant 16-88807362-C-T is Benign according to our data. Variant chr16-88807362-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434677.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0004 (61/152360) while in subpopulation SAS AF= 0.0087 (42/4830). AF 95% confidence interval is 0.00661. There are 1 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDT1 | NM_030928.4 | c.1357C>T | p.Arg453Trp | missense_variant | 9/10 | ENST00000301019.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDT1 | ENST00000301019.9 | c.1357C>T | p.Arg453Trp | missense_variant | 9/10 | 1 | NM_030928.4 | P1 | |
CDT1 | ENST00000569140.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000394 AC: 60AN: 152242Hom.: 1 Cov.: 34
GnomAD3 genomes
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34
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GnomAD3 exomes AF: 0.00127 AC: 313AN: 246838Hom.: 5 AF XY: 0.00171 AC XY: 230AN XY: 134590
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GnomAD4 exome AF: 0.000712 AC: 1040AN: 1460212Hom.: 16 Cov.: 33 AF XY: 0.00101 AC XY: 732AN XY: 726436
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GnomAD4 genome ? AF: 0.000400 AC: 61AN: 152360Hom.: 1 Cov.: 34 AF XY: 0.000550 AC XY: 41AN XY: 74496
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ExAC
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179
Asia WGS
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3478
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 15, 2016 | - - |
Meier-Gorlin syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at