Variant chr1-20618510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001785.3(CDA):c.383C>T(p.Thr128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,613,726 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

CDA
NM_001785.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

CDA (HGNC:1712): (cytidine deaminase) This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. It is one of several deaminases responsible for maintaining the cellular pyrimidine pool. Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias. [provided by RefSeq, Jul 2008]

CDA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15498427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDA	NM_001785.3 linkuse as main transcript	c.383C>T	p.Thr128Met	missense_variant	4/4	ENST00000375071.4	NP_001776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDA	ENST00000375071.4 linkuse as main transcript	c.383C>T	p.Thr128Met	missense_variant	4/4	1	NM_001785.3	ENSP00000364212	P1
CDA	ENST00000461985.1 linkuse as main transcript	n.369C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251286

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1461586

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000824

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000532

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000550

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.383C>T (p.T128M) alteration is located in exon 4 (coding exon 4) of the CDA gene. This alteration results from a C to T substitution at nucleotide position 383, causing the threonine (T) at amino acid position 128 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.20

MVP

0.39

MPC

0.33

ClinPred

0.15

GERP RS

4.8

Varity_R

0.28

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over