chr3-182947280-T-A

Variant names:

• chr3-182947280-T-A
• NM_020640.4:c.658A>T

Variant summary

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

The NM_020640.4(DCUN1D1):​c.658A>T​(p.Ser220Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DCUN1D1 NM_020640.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	NM_020640.4	MANE Select	c.658A>T	p.Ser220Cys	missense	Exon 6 of 7	NP_065691.2
	DCUN1D1	NM_001308101.2		c.613A>T	p.Ser205Cys	missense	Exon 6 of 7	NP_001295030.1	C9JVE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	ENST00000292782.9	TSL:1 MANE Select	c.658A>T	p.Ser220Cys	missense	Exon 6 of 7	ENSP00000292782.4	Q96GG9
	DCUN1D1	ENST00000632685.1	TSL:1	c.613A>T	p.Ser205Cys	missense	Exon 6 of 7	ENSP00000488427.1	C9JVE2
	DCUN1D1	ENST00000925548.1		c.658A>T	p.Ser220Cys	missense	Exon 6 of 7	ENSP00000595607.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458058 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725144

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.00 AC: 0 AN: 44038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110910

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.30
Sift	Benign	0.10	T
Sift4G	Benign	0.092	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.59		Loss of glycosylation at S220 (P = 0.0375)
MVP		0.64
MPC		1.0
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.76
Mutation Taster		=44/56	disease causing

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

hg19: chr3-182665068;