NM_020640.4:c.302G>C

Variant names:

• chr3-182963968-C-G
• rs1727533258
• NM_020640.4:c.302G>C

Variant summary

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

The NM_020640.4(DCUN1D1):​c.302G>C​(p.Ser101Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000021 (0 hom.)
• Consequence: DCUN1D1 NM_020640.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2512943).

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.302G>C	p.Ser101Thr	missense	Exon 3 of 7	NP_065691.2
	DCUN1D1	NM_001308101.2		c.257G>C	p.Ser86Thr	missense	Exon 3 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.302G>C	p.Ser101Thr	missense	Exon 3 of 7	ENSP00000292782.4	Q96GG9
	DCUN1D1	ENST00000632685.1	TSL:1	c.257G>C	p.Ser86Thr	missense	Exon 3 of 7	ENSP00000488427.1	C9JVE2
	DCUN1D1	ENST00000925548.1		c.302G>C	p.Ser101Thr	missense	Exon 3 of 7	ENSP00000595607.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461710 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111890

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.065
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.31
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		5.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.17
Sift	Benign	0.62	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.34		Loss of stability (P = 0.2808)
MVP		0.41
MPC		0.79
ClinPred		0.81	D
GERP RS		5.1
Varity_R		0.39
gMVP		0.49
Mutation Taster		=69/31	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: rs1727533258; hg19: chr3-182681756;