chr13-49267733-C-A

Position:

• chr13-49267733-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030911.4(CDADC1):​c.674C>A​(p.Thr225Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDADC1 NM_030911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01

Genes affected

CDADC1 (HGNC:20299): (cytidine and dCMP deaminase domain containing 1) Enables several functions, including cytidine deaminase activity; importin-alpha family protein binding activity; and protein homodimerization activity. Involved in DNA cytosine deamination and cytidine deamination. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CDADC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04673949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDADC1	NM_030911.4	c.674C>A	p.Thr225Asn	missense_variant	5/10	ENST00000251108.10	NP_112173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDADC1	ENST00000251108.10	c.674C>A	p.Thr225Asn	missense_variant	5/10	1	NM_030911.4	ENSP00000251108.6
CDADC1	ENST00000466868.1	n.625C>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.674C>A (p.T225N) alteration is located in exon 5 (coding exon 5) of the CDADC1 gene. This alteration results from a C to A substitution at nucleotide position 674, causing the threonine (T) at amino acid position 225 to be replaced by an asparagine (N). 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	0.083
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.22
DANN	Benign	0.86
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.032
Sift	Benign	0.048	D
Sift4G	Uncertain	0.054	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.24		Loss of catalytic residue at T225 (P = 0.0442);
MVP		0.11
MPC		0.38
ClinPred		0.042	T
GERP RS		-6.0
Varity_R		0.074
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-49841869;