4-51863458-T-C

Variant names:

• chr4-51863458-T-C
• NM_001040402.3:c.47T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040402.3(DCUN1D4):​c.47T>C​(p.Leu16Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCUN1D4 NM_001040402.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30

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.47T>C	p.Leu16Pro	missense_variant	Exon 2 of 11	ENST00000334635.10	NP_001035492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCUN1D4	ENST00000334635.10	c.47T>C	p.Leu16Pro	missense_variant	Exon 2 of 11	1	NM_001040402.3	ENSP00000334625.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47T>C (p.L16P) alteration is located in exon 2 (coding exon 2) of the DCUN1D4 gene. This alteration results from a T to C substitution at nucleotide position 47, causing the leucine (L) at amino acid position 16 to be replaced by a proline (P). 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	0.69
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.029	T;.;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.7	L;L;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.42	N;N;N;N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.99	D;D;.;.
Vest4		0.94
MutPred		0.45		Gain of disorder (P = 0.0359);Gain of disorder (P = 0.0359);.;.;
MVP		0.64
MPC		0.94
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.65
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-52729624;