4-182894535-A-G

Position:

• chr4-182894535-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001921.3(DCTD):​c.315T>C​(p.Val105=) 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTD	NM_001921.3	c.315T>C	p.Val105=	synonymous_variant	4/6	ENST00000438320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTD	ENST00000438320.7	c.315T>C	p.Val105=	synonymous_variant	4/6	1	NM_001921.3	P1

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

GnomAD3 exomes AF: 0.283 AC: 71233 AN: 251298 Hom.: 11014 AF XY: 0.284 AC XY: 38626 AN XY: 135810

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 SAS exome AF: 0.251

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

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.305

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

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.291

Alfa AF: 0.311 Hom.: 4957

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.3
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4742; hg19: chr4-183815688; COSMIC: COSV63866949; COSMIC: COSV63866949;