14-69053935-A-T

Variant names:

• chr14-69053935-A-T
• NM_003861.3:c.2751T>A

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.2751T>A​(p.Ser917Arg) 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. 15/22 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: 1.25
• 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=0.11209142).

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.2751T>A	p.Ser917Arg	missense	Exon 9 of 9	NP_003852.1	Q96JK2-1
	DCAF5	NM_001284206.1		c.2748T>A	p.Ser916Arg	missense	Exon 9 of 9	NP_001271135.1	Q96JK2-3
	DCAF5	NM_001284207.1		c.2505T>A	p.Ser835Arg	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.2751T>A	p.Ser917Arg	missense	Exon 9 of 9	ENSP00000341351.5	Q96JK2-1
	DCAF5	ENST00000557386.5	TSL:1	c.2748T>A	p.Ser916Arg	missense	Exon 9 of 9	ENSP00000451845.1	Q96JK2-3
	DCAF5	ENST00000554215.5	TSL:1	c.2505T>A	p.Ser835Arg	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	0.21
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.058	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.30		Gain of solvent accessibility (P = 0.0014)
MVP		0.40
MPC		0.39
ClinPred		0.42	T
GERP RS		2.8
Varity_R		0.13
gMVP		0.10
Mutation Taster		=91/9	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: chr14-69520652;