NM_024040.3:c.335A>C

Variant names:

• chr10-102424340-T-G
• NM_024040.3:c.335A>C

Variant summary

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

The NM_024040.3(CUEDC2):​c.335A>C​(p.Glu112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CUEDC2 NM_024040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

Genes affected

CUEDC2 (HGNC:28352): (CUE domain containing 2) Predicted to enable ubiquitin binding activity. Acts upstream of or within negative regulation of cytokine production involved in inflammatory response and negative regulation of macrophage cytokine production. Located in cytosol; nuclear membrane; and nucleoplasm. [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=0.08766544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024040.3. 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
	CUEDC2	NM_024040.3	MANE Select	c.335A>C	p.Glu112Ala	missense	Exon 5 of 9	NP_076945.2	Q9H467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUEDC2	ENST00000369937.5	TSL:1 MANE Select	c.335A>C	p.Glu112Ala	missense	Exon 5 of 9	ENSP00000358953.4	Q9H467
	CUEDC2	ENST00000888785.1		c.335A>C	p.Glu112Ala	missense	Exon 5 of 9	ENSP00000558844.1
	CUEDC2	ENST00000925790.1		c.335A>C	p.Glu112Ala	missense	Exon 5 of 9	ENSP00000595849.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.39	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.14		Loss of loop (P = 0.0203)
MVP		0.85
MPC		0.45
ClinPred		0.055	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.37
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr10-104184097;