4-51913306-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCUN1D4	NM_001040402.3	c.737T>C	p.Val246Ala	missense_variant	Exon 10 of 11	ENST00000334635.10	NP_001035492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCUN1D4	ENST00000334635.10	c.737T>C	p.Val246Ala	missense_variant	Exon 10 of 11	1	NM_001040402.3	ENSP00000334625.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248406 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134272

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.737T>C (p.V246A) alteration is located in exon 10 (coding exon 10) of the DCUN1D4 gene. This alteration results from a T to C substitution at nucleotide position 737, causing the valine (V) at amino acid position 246 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.1	L;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D;N;D;N
REVEL	Uncertain	0.37
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.81	P;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1451986820; hg19: chr4-52779472;