rs9990999

Positions:

• chr4-182902820-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTD	NM_001921.3	c.245-8215C>T		intron_variant		ENST00000438320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTD	ENST00000438320.7	c.245-8215C>T		intron_variant		1	NM_001921.3	P1

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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.332

Alfa AF: 0.405 Hom.: 7173

Bravo AF: 0.350

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs9990999; hg19: chr4-183823973;