dbSNP rs144843732: CDT1:p.Glu544Gly (chr16-88808268-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030928.4(CDT1):c.1631A>G(p.Glu544Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E544D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDT1
NM_030928.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

0 publications found

Variant links:

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]

CDT1 Gene-Disease associations (from GenCC):

Meier-Gorlin syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
Meier-Gorlin syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2088907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDT1	NM_030928.4 link	c.1631A>G	p.Glu544Gly	missense_variant	Exon 10 of 10	ENST00000301019.9	NP_112190.2	Q9H211

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDT1	ENST00000301019.9 link	c.1631A>G	p.Glu544Gly	missense_variant	Exon 10 of 10	1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1436858

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33064

American (AMR)

AF:

0.00

AC:

AN:

40786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25568

East Asian (EAS)

AF:

0.00

AC:

AN:

38628

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100214

Other (OTH)

AF:

0.00

AC:

AN:

59442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.81

PhyloP100

1.2

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.017

Polyphen

0.91

Vest4

0.16

MutPred

0.19

Loss of helix (P = 0.0167);

MVP

0.80

MPC

0.017

ClinPred

0.80

GERP RS

0.22

Varity_R

0.21

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over