4-51863697-G-C

Variant names:

• chr4-51863697-G-C
• rs758053478
• NM_001040402.3:c.124G>C

Variant summary

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

The NM_001040402.3(DCUN1D4):​c.124G>C​(p.Asp42His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D42N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCUN1D4 NM_001040402.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25454608).

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.124G>C	p.Asp42His	missense	Exon 3 of 11	NP_001035492.1	Q92564-1
	DCUN1D4	NM_001287755.1		c.256G>C	p.Asp86His	missense	Exon 3 of 11	NP_001274684.1	Q92564-3
	DCUN1D4	NM_015115.4		c.124G>C	p.Asp42His	missense	Exon 3 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.124G>C	p.Asp42His	missense	Exon 3 of 11	ENSP00000334625.5	Q92564-1
	DCUN1D4	ENST00000381441.7	TSL:1	c.124G>C	p.Asp42His	missense	Exon 3 of 10	ENSP00000370850.3	Q92564-2
	DCUN1D4	ENST00000451288.6	TSL:2	c.256G>C	p.Asp86His	missense	Exon 3 of 11	ENSP00000389900.2	Q92564-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.090		Gain of glycosylation at S47 (P = 0.0858)
MVP		0.57
MPC		0.56
ClinPred		0.89	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.32
Mutation Taster		=81/19	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: rs758053478; hg19: chr4-52729863;