chr3-182963952-C-T

Variant names:

• chr3-182963952-C-T
• rs4859146
• NM_020640.4:c.318G>A

Variant summary

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

The NM_020640.4(DCUN1D1):​c.318G>A​(p.Ala106Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,228 control chromosomes in the GnomAD database, including 446,850 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 0.73 (41047 hom., cov: 32)
  • Exomes 𝑓: 0.74 (405803 hom.)
• Consequence: DCUN1D1 NM_020640.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 24 publications found

Genes affected

DCUN1D1 (HGNC:18184): (defective in cullin neddylation 1 domain containing 1) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation and regulation of protein ubiquitination. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	NM_020640.4	MANE Select	c.318G>A	p.Ala106Ala	synonymous	Exon 3 of 7	NP_065691.2
	DCUN1D1	NM_001308101.2		c.273G>A	p.Ala91Ala	synonymous	Exon 3 of 7	NP_001295030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	ENST00000292782.9	TSL:1 MANE Select	c.318G>A	p.Ala106Ala	synonymous	Exon 3 of 7	ENSP00000292782.4
	DCUN1D1	ENST00000632685.1	TSL:1	c.273G>A	p.Ala91Ala	synonymous	Exon 3 of 7	ENSP00000488427.1
	DCUN1D1	ENST00000925548.1		c.318G>A	p.Ala106Ala	synonymous	Exon 3 of 7	ENSP00000595607.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110586 AN: 152008 Hom.: 41012 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.717

GnomAD2 exomes AF: 0.687 AC: 172491 AN: 251252 AF XY: 0.686

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.634

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.759

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.738 AC: 1078653 AN: 1461102 Hom.: 405803 Cov.: 43 AF XY: 0.735 AC XY: 534010 AN XY: 726910

African (AFR) AF: 0.745 AC: 24923 AN: 33472

American (AMR) AF: 0.667 AC: 29791 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 16608 AN: 26116

East Asian (EAS) AF: 0.229 AC: 9080 AN: 39664

South Asian (SAS) AF: 0.621 AC: 53538 AN: 86176

European-Finnish (FIN) AF: 0.770 AC: 41127 AN: 53380

Middle Eastern (MID) AF: 0.669 AC: 3857 AN: 5766

European-Non Finnish (NFE) AF: 0.771 AC: 856417 AN: 1111478

Other (OTH) AF: 0.717 AC: 43312 AN: 60366

GnomAD4 genome AF: 0.727 AC: 110663 AN: 152126 Hom.: 41047 Cov.: 32 AF XY: 0.722 AC XY: 53723 AN XY: 74358

African (AFR) AF: 0.743 AC: 30822 AN: 41480

American (AMR) AF: 0.682 AC: 10431 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2188 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5168

South Asian (SAS) AF: 0.610 AC: 2940 AN: 4818

European-Finnish (FIN) AF: 0.772 AC: 8165 AN: 10580

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52275 AN: 68006

Other (OTH) AF: 0.715 AC: 1510 AN: 2112

Alfa AF: 0.750 Hom.: 22907

Bravo AF: 0.720

Asia WGS AF: 0.473 AC: 1649 AN: 3478

EpiCase AF: 0.760

EpiControl AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		-2.4
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: rs4859146; hg19: chr3-182681740; COSMIC: COSV53044616; COSMIC: COSV53044616;