16-20862376-C-A

Variant names:

• chr16-20862376-C-A
• rs777603187
• NM_173475.4:c.163G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173475.4(DCUN1D3):​c.163G>T​(p.Gly55Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G55R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCUN1D3 NM_173475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

DCUN1D3 (HGNC:28734): (defective in cullin neddylation 1 domain containing 3) Enables cullin family protein binding activity. Involved in several processes, including negative regulation of G1/S transition of mitotic cell cycle; regulation of protein neddylation; and response to UV-C. Located in nucleus; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERI2 (HGNC:30541): (ERI1 exoribonuclease family member 2) Predicted to enable 3'-5'-exoribonuclease activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173475.4. 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
	DCUN1D3	NM_173475.4	MANE Select	c.163G>T	p.Gly55Trp	missense	Exon 2 of 3	NP_775746.1	Q8IWE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D3	ENST00000324344.9	TSL:1 MANE Select	c.163G>T	p.Gly55Trp	missense	Exon 2 of 3	ENSP00000319482.3	Q8IWE4
	DCUN1D3	ENST00000563934.1	TSL:5	c.163G>T	p.Gly55Trp	missense	Exon 2 of 3	ENSP00000454762.1	Q8IWE4
	DCUN1D3	ENST00000900856.1		c.163G>T	p.Gly55Trp	missense	Exon 3 of 4	ENSP00000570915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0077	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.28		Loss of sheet (P = 0.0054)
MVP		0.45
MPC		1.5
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.50

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: rs777603187; hg19: chr16-20873698;