chr4-182894535-A-G

Variant names:

• chr4-182894535-A-G
• rs4742
• NM_001921.3:c.315T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001921.3(DCTD):​c.315T>C​(p.Val105Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,612,170 control chromosomes in the GnomAD database, including 79,725 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 0.35 (9942 hom., cov: 33)
  • Exomes 𝑓: 0.30 (69783 hom.)
• Consequence: DCTD NM_001921.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 31 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]

ENSG00000303565 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=0.264 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.315T>C	p.Val105Val	synonymous	Exon 4 of 6	NP_001912.2	P32321-1
	DCTD	NM_001012732.2		c.348T>C	p.Val116Val	synonymous	Exon 4 of 6	NP_001012750.1	P32321-2
	DCTD	NM_001351743.2		c.315T>C	p.Val105Val	synonymous	Exon 6 of 8	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.315T>C	p.Val105Val	synonymous	Exon 4 of 6	ENSP00000398194.2	P32321-1
	DCTD	ENST00000357067.7	TSL:1	c.348T>C	p.Val116Val	synonymous	Exon 4 of 6	ENSP00000349576.3	P32321-2
	DCTD	ENST00000507631.5	TSL:1	n.*53T>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000425287.1	D6RD72

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52803 AN: 152036 Hom.: 9922 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.283 AC: 71233 AN: 251298 AF XY: 0.284

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.304 AC: 444370 AN: 1460016 Hom.: 69783 Cov.: 32 AF XY: 0.303 AC XY: 219899 AN XY: 726340

African (AFR) AF: 0.504 AC: 16867 AN: 33438

American (AMR) AF: 0.149 AC: 6643 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6132 AN: 26120

East Asian (EAS) AF: 0.208 AC: 8247 AN: 39682

South Asian (SAS) AF: 0.251 AC: 21648 AN: 86212

European-Finnish (FIN) AF: 0.340 AC: 18137 AN: 53406

Middle Eastern (MID) AF: 0.267 AC: 1540 AN: 5768

European-Non Finnish (NFE) AF: 0.312 AC: 346753 AN: 1110350

Other (OTH) AF: 0.305 AC: 18403 AN: 60330

GnomAD4 genome AF: 0.347 AC: 52859 AN: 152154 Hom.: 9942 Cov.: 33 AF XY: 0.343 AC XY: 25530 AN XY: 74374

African (AFR) AF: 0.502 AC: 20818 AN: 41502

American (AMR) AF: 0.219 AC: 3354 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.236 AC: 1221 AN: 5184

South Asian (SAS) AF: 0.250 AC: 1208 AN: 4826

European-Finnish (FIN) AF: 0.340 AC: 3596 AN: 10584

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20873 AN: 67976

Other (OTH) AF: 0.291 AC: 616 AN: 2114

Alfa AF: 0.285 Hom.: 5561

Bravo AF: 0.344

Asia WGS AF: 0.286 AC: 992 AN: 3478

EpiCase AF: 0.293

EpiControl AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.3
DANN	Benign	0.57
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs4742; hg19: chr4-183815688; COSMIC: COSV63866949; COSMIC: COSV63866949;