rs6823077

Variant names:

• chr4-182912789-A-C
• rs6823077
• NM_001921.3:c.244+2134T>G

Variant summary

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

The NM_001921.3(DCTD):​c.244+2134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,908 control chromosomes in the GnomAD database, including 17,861 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 0.48 (17861 hom., cov: 32)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 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.244+2134T>G		intron	N/A	NP_001912.2	P32321-1
	DCTD	NM_001012732.2		c.277+2134T>G		intron	N/A	NP_001012750.1	P32321-2
	DCTD	NM_001351743.2		c.244+2134T>G		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.244+2134T>G		intron	N/A	ENSP00000398194.2	P32321-1
	DCTD	ENST00000357067.7	TSL:1	c.277+2134T>G		intron	N/A	ENSP00000349576.3	P32321-2
	DCTD	ENST00000507631.5	TSL:1	n.108+2672T>G		intron	N/A	ENSP00000425287.1	D6RD72

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72309 AN: 151788 Hom.: 17837 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.476 AC: 72379 AN: 151908 Hom.: 17861 Cov.: 32 AF XY: 0.474 AC XY: 35185 AN XY: 74252

African (AFR) AF: 0.593 AC: 24575 AN: 41436

American (AMR) AF: 0.325 AC: 4962 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1555 AN: 5134

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4814

European-Finnish (FIN) AF: 0.523 AC: 5526 AN: 10556

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31371 AN: 67924

Other (OTH) AF: 0.422 AC: 891 AN: 2110

Alfa AF: 0.454 Hom.: 51748

Bravo AF: 0.466

Asia WGS AF: 0.385 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.93
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: rs6823077; hg19: chr4-183833942;