rs1451986820

Variant names:

• chr4-51913306-T-C
• rs1451986820
• NM_001040402.3:c.737T>C

Variant summary

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

The NM_001040402.3(DCUN1D4):​c.737T>C​(p.Val246Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,344 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: DCUN1D4 NM_001040402.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27
• Publications: 0 publications found

Genes affected

DCUN1D4 (HGNC:28998): (defective in cullin neddylation 1 domain containing 4) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation. Located in nucleus. [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_001040402.3. 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
	DCUN1D4	NM_001040402.3	MANE Select	c.737T>C	p.Val246Ala	missense	Exon 10 of 11	NP_001035492.1	Q92564-1
	DCUN1D4	NM_001287755.1		c.869T>C	p.Val290Ala	missense	Exon 10 of 11	NP_001274684.1	Q92564-3
	DCUN1D4	NM_015115.4		c.632T>C	p.Val211Ala	missense	Exon 9 of 10	NP_055930.2	Q92564-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D4	ENST00000334635.10	TSL:1 MANE Select	c.737T>C	p.Val246Ala	missense	Exon 10 of 11	ENSP00000334625.5	Q92564-1
	DCUN1D4	ENST00000381441.7	TSL:1	c.632T>C	p.Val211Ala	missense	Exon 9 of 10	ENSP00000370850.3	Q92564-2
	DCUN1D4	ENST00000451288.6	TSL:2	c.869T>C	p.Val290Ala	missense	Exon 10 of 11	ENSP00000389900.2	Q92564-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248406 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455344 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723998

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 85254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108042

Other (OTH) AF: 0.00 AC: 0 AN: 60102

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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.37
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.81	P
Vest4		0.79
MutPred		0.49		Loss of stability (P = 0.0247)
MVP		0.70
MPC		0.58
ClinPred		0.71	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.49
Mutation Taster		=13/87	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

dbSNP: rs1451986820; hg19: chr4-52779472;