NM_001921.3:c.409G>A

Variant names:

• chr4-182893080-C-T
• rs1297073291
• NM_001921.3:c.409G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001921.3(DCTD):​c.409G>A​(p.Glu137Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DCTD NM_001921.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22884542).

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.409G>A	p.Glu137Lys	missense	Exon 5 of 6	NP_001912.2	P32321-1
	DCTD	NM_001012732.2		c.442G>A	p.Glu148Lys	missense	Exon 5 of 6	NP_001012750.1	P32321-2
	DCTD	NM_001351743.2		c.409G>A	p.Glu137Lys	missense	Exon 7 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.409G>A	p.Glu137Lys	missense	Exon 5 of 6	ENSP00000398194.2	P32321-1
	DCTD	ENST00000357067.7	TSL:1	c.442G>A	p.Glu148Lys	missense	Exon 5 of 6	ENSP00000349576.3	P32321-2
	DCTD	ENST00000507631.5	TSL:1	n.*147G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000425287.1	D6RD72

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 249878 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000635

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460596 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726538

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111268

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.072
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.40	T
Sift4G	Benign	0.45	T
Polyphen		0.010	B
Vest4		0.75
MutPred		0.37		Loss of helix (P = 0.0196)
MVP		0.71
MPC		0.25
ClinPred		0.32	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.82
Mutation Taster		=66/34	polymorphism

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: rs1297073291; hg19: chr4-183814233;