4-51891817-C-T

Variant names:

• chr4-51891817-C-T
• rs767827240
• NM_001040402.3:c.472C>T

Variant summary

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

The NM_001040402.3(DCUN1D4):​c.472C>T​(p.Leu158Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCUN1D4 NM_001040402.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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.472C>T	p.Leu158Leu	synonymous	Exon 7 of 11	NP_001035492.1	Q92564-1
	DCUN1D4	NM_001287755.1		c.604C>T	p.Leu202Leu	synonymous	Exon 7 of 11	NP_001274684.1	Q92564-3
	DCUN1D4	NM_015115.4		c.472C>T	p.Leu158Leu	synonymous	Exon 7 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.472C>T	p.Leu158Leu	synonymous	Exon 7 of 11	ENSP00000334625.5	Q92564-1
	DCUN1D4	ENST00000381441.7	TSL:1	c.472C>T	p.Leu158Leu	synonymous	Exon 7 of 10	ENSP00000370850.3	Q92564-2
	DCUN1D4	ENST00000510808.1	TSL:4	c.11C>T	p.Ser4Phe	missense	Exon 1 of 4	ENSP00000426048.1	H0YA35

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726656

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111336

Other (OTH) AF: 0.0000166 AC: 1 AN: 60332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.0072	T
Eigen	Benign	0.030
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.82	T
PhyloP100		1.2
PROVEAN	Benign	2.7	N
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
MutPred		0.31		Loss of disorder (P = 0)
MVP		0.34
ClinPred		0.54	D
GERP RS		4.2
PromoterAI		-0.0037	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767827240; hg19: chr4-52757983;