3-182965756-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_020640.4(DCUN1D1):c.4-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,599,378 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (18 hom.)
• Consequence: DCUN1D1 NM_020640.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001531
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.23

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 3-182965756-A-G is Benign according to our data. Variant chr3-182965756-A-G is described in ClinVar as [Benign]. Clinvar id is 769618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000988 (1430/1447042) while in subpopulation AMR AF= 0.0175 (765/43698). AF 95% confidence interval is 0.0165. There are 18 homozygotes in gnomad4_exome. There are 609 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd at 277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCUN1D1	NM_020640.4	c.4-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000292782.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCUN1D1	ENST00000292782.9	c.4-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020640.4	P1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152218 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00268 AC: 662 AN: 247296 Hom.: 6 AF XY: 0.00208 AC XY: 279 AN XY: 134038

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00477

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00317

GnomAD4 exome AF: 0.000988 AC: 1430 AN: 1447042 Hom.: 18 Cov.: 28 AF XY: 0.000846 AC XY: 609 AN XY: 719902

Gnomad4 AFR exome AF: 0.000639

Gnomad4 AMR exome AF: 0.0175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0145

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000173

Gnomad4 OTH exome AF: 0.000854

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152336 Hom.: 3 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74496

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000573 Hom.: 0

Bravo AF: 0.00306

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	13
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0020
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

Publications

LitVar

Other links and lift over

dbSNP: rs143412605; hg19: chr3-182683544; COSMIC: COSV53045754;