Variant 13-49280608-A-C 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_030911.4(CDADC1):c.1320A>C(p.Gln440His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDADC1
NM_030911.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0760

Variant links:

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 links:

CDADC1 (HGNC:):

CDADC1 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=0.075286716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDADC1	NM_030911.4 linkuse as main transcript	c.1320A>C	p.Gln440His	missense_variant	8/10	ENST00000251108.10	NP_112173.1	Q9BWV3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDADC1	ENST00000251108.10 linkuse as main transcript	c.1320A>C	p.Gln440His	missense_variant	8/10	1	NM_030911.4	ENSP00000251108.6		Q9BWV3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245276

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133206

show subpopulations

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 SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450324

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

722002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 12, 2021

The c.1320A>C (p.Q440H) alteration is located in exon 8 (coding exon 8) of the CDADC1 gene. This alteration results from a A to C substitution at nucleotide position 1320, causing the glutamine (Q) at amino acid position 440 to be replaced by a histidine (H). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.063

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0074

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.36

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

REVEL

Benign

0.13

Sift

Benign

0.34

Sift4G

Benign

0.41

Polyphen

0.084

Vest4

0.27

MutPred

0.45

Gain of methylation at K439 (P = 0.1543);

MVP

0.19

MPC

0.39

ClinPred

0.13

GERP RS

-2.2

Varity_R

0.20

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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