NM_001785.3:c.208G>T

Variant names:

• chr1-20604981-G-T
• rs60369023
• NM_001785.3:c.208G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001785.3(CDA):​c.208G>T​(p.Ala70Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A70A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDA NM_001785.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.94
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001785.3. 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
	CDA	NM_001785.3	MANE Select	c.208G>T	p.Ala70Ser	missense	Exon 2 of 4	NP_001776.1	P32320

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDA	ENST00000375071.4	TSL:1 MANE Select	c.208G>T	p.Ala70Ser	missense	Exon 2 of 4	ENSP00000364212.3	P32320
	CDA	ENST00000904801.1		c.208G>T	p.Ala70Ser	missense	Exon 2 of 5	ENSP00000574860.1
	CDA	ENST00000916580.1		c.238G>T	p.Ala80Ser	missense	Exon 2 of 4	ENSP00000586639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		8.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.77		Gain of disorder (P = 0.0437)
MVP		0.72
MPC		0.42
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.75
gMVP		0.79
Mutation Taster		=60/40	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: rs60369023; hg19: chr1-20931474;