rs9990999

Variant names:

• chr4-182902820-G-A
• rs9990999
• NM_001921.3:c.245-8215C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001921.3(DCTD):​c.245-8215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,948 control chromosomes in the GnomAD database, including 10,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10461 hom., cov: 32)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 5 publications found

Genes affected

DCTD (HGNC:2710): (dCMP deaminase) The protein encoded by this gene catalyzes the deamination of dCMP to dUMP, the nucleotide substrate for thymidylate synthase. The encoded protein is allosterically activated by dCTP and inhibited by dTTP, and is found as a homohexamer. This protein uses zinc as a cofactor for its activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001921.3. 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
	DCTD	NM_001921.3	MANE Select	c.245-8215C>T		intron	N/A	NP_001912.2	P32321-1
	DCTD	NM_001012732.2		c.278-8215C>T		intron	N/A	NP_001012750.1	P32321-2
	DCTD	NM_001351743.2		c.245-8215C>T		intron	N/A	NP_001338672.1	P32321-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTD	ENST00000438320.7	TSL:1 MANE Select	c.245-8215C>T		intron	N/A	ENSP00000398194.2	P32321-1
	DCTD	ENST00000357067.7	TSL:1	c.278-8215C>T		intron	N/A	ENSP00000349576.3	P32321-2
	DCTD	ENST00000507631.5	TSL:1	n.109-8215C>T		intron	N/A	ENSP00000425287.1	D6RD72

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55405 AN: 151830 Hom.: 10459 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55426 AN: 151948 Hom.: 10461 Cov.: 32 AF XY: 0.361 AC XY: 26827 AN XY: 74242

African (AFR) AF: 0.314 AC: 13018 AN: 41458

American (AMR) AF: 0.245 AC: 3738 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 953 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5154

South Asian (SAS) AF: 0.332 AC: 1602 AN: 4820

European-Finnish (FIN) AF: 0.401 AC: 4223 AN: 10536

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28823 AN: 67920

Other (OTH) AF: 0.332 AC: 700 AN: 2110

Alfa AF: 0.405 Hom.: 7874

Bravo AF: 0.350

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs9990999; hg19: chr4-183823973;