3-182964065-T-G

Variant names:

• chr3-182964065-T-G
• rs4859147
• NM_020640.4:c.221-16A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_020640.4(DCUN1D1):​c.221-16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,447,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: DCUN1D1 NM_020640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• 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: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.221-16A>C		intron	N/A	NP_065691.2
	DCUN1D1	NM_001308101.2		c.176-16A>C		intron	N/A	NP_001295030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	ENST00000292782.9	TSL:1 MANE Select	c.221-16A>C		intron	N/A	ENSP00000292782.4
	DCUN1D1	ENST00000632685.1	TSL:1	c.176-16A>C		intron	N/A	ENSP00000488427.1
	DCUN1D1	ENST00000460412.6	TSL:3	c.176-16A>C		intron	N/A	ENSP00000419440.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1447064 Hom.: 0 Cov.: 26 AF XY: 0.00000417 AC XY: 3 AN XY: 719786

African (AFR) AF: 0.00 AC: 0 AN: 33164

American (AMR) AF: 0.00 AC: 0 AN: 43600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 85078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000454 AC: 5 AN: 1101524

Other (OTH) AF: 0.00 AC: 0 AN: 59768

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.36
PhyloP100		-0.11

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: rs4859147; hg19: chr3-182681853;