rs751315293

Variant names:

• chr16-88808189-G-A
• rs751315293
• NM_030928.4:c.1552G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-88808189-G-A
• chr16-88808189-G-C
• chr16-88808189-G-T

Variant summary

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

The NM_030928.4(CDT1):​c.1552G>A​(p.Asp518Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000502 in 1,612,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: CDT1 NM_030928.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 5.95
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Meier-Gorlin syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	NM_030928.4	MANE Select	c.1552G>A	p.Asp518Asn	missense	Exon 10 of 10	NP_112190.2	Q9H211

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDT1	ENST00000301019.9	TSL:1 MANE Select	c.1552G>A	p.Asp518Asn	missense	Exon 10 of 10	ENSP00000301019.4	Q9H211
	CDT1	ENST00000929785.1		c.1573G>A	p.Asp525Asn	missense	Exon 10 of 10	ENSP00000599844.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152240 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000644 AC: 16 AN: 248382 AF XY: 0.0000963

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000281

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000514 AC: 75 AN: 1460440 Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41 AN XY: 726510

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86206

European-Finnish (FIN) AF: 0.000268 AC: 14 AN: 52214

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111908

Other (OTH) AF: 0.000133 AC: 8 AN: 60374

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152240 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000744 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.050
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.52		Gain of MoRF binding (P = 0.0555)
MVP		0.77
MPC		0.018
ClinPred		0.34	T
GERP RS		4.5
Varity_R		0.35
gMVP		0.48
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs751315293; hg19: chr16-88874597;