NM_003861.3:c.2236G>T

Variant names:

• chr14-69054450-C-A
• NM_003861.3:c.2236G>T

Variant summary

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

The NM_003861.3(DCAF5):​c.2236G>T​(p.Gly746Cys) 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: DCAF5 NM_003861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.883
• Publications: 0 publications found

Genes affected

DCAF5 (HGNC:20224): (DDB1 and CUL4 associated factor 5) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [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=0.15553981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003861.3. 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
	DCAF5	NM_003861.3	MANE Select	c.2236G>T	p.Gly746Cys	missense	Exon 9 of 9	NP_003852.1	Q96JK2-1
	DCAF5	NM_001284206.1		c.2233G>T	p.Gly745Cys	missense	Exon 9 of 9	NP_001271135.1	Q96JK2-3
	DCAF5	NM_001284207.1		c.1990G>T	p.Gly664Cys	missense	Exon 9 of 9	NP_001271136.1	Q96JK2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF5	ENST00000341516.10	TSL:1 MANE Select	c.2236G>T	p.Gly746Cys	missense	Exon 9 of 9	ENSP00000341351.5	Q96JK2-1
	DCAF5	ENST00000557386.5	TSL:1	c.2233G>T	p.Gly745Cys	missense	Exon 9 of 9	ENSP00000451845.1	Q96JK2-3
	DCAF5	ENST00000554215.5	TSL:1	c.1990G>T	p.Gly664Cys	missense	Exon 9 of 9	ENSP00000451551.1	Q96JK2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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	0.084
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.88
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.053	T
Sift4G	Uncertain	0.060	T
Polyphen		0.83	P
Vest4		0.21
MutPred		0.28		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.25
MPC		0.23
ClinPred		0.40	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.048
Mutation Taster		=89/11	polymorphism

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

hg19: chr14-69521167;