16-88807477-G-T

Position:

• chr16-88807477-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030928.4(CDT1):​c.1472G>T​(p.Ser491Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,578 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S491N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDT1 NM_030928.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDT1	NM_030928.4	c.1472G>T	p.Ser491Ile	missense_variant	9/10	ENST00000301019.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDT1	ENST00000301019.9	c.1472G>T	p.Ser491Ile	missense_variant	9/10	1	NM_030928.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248726 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460578 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726588

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.94	P
Vest4		0.52
MutPred		0.46		Loss of disorder (P = 0.0171);
MVP		0.86
MPC		0.079
ClinPred		0.94	D
GERP RS		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.64
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs146199695; hg19: chr16-88873885;