NM_003861.3:c.2795A>C

Variant names:

• chr14-69053891-T-G
• rs754319970
• NM_003861.3:c.2795A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003861.3(DCAF5):​c.2795A>C​(p.Glu932Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCAF5 NM_003861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12902501).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.2795A>C	p.Glu932Ala	missense	Exon 9 of 9	NP_003852.1	Q96JK2-1
	DCAF5	NM_001284206.1		c.2792A>C	p.Glu931Ala	missense	Exon 9 of 9	NP_001271135.1	Q96JK2-3
	DCAF5	NM_001284207.1		c.2549A>C	p.Glu850Ala	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.2795A>C	p.Glu932Ala	missense	Exon 9 of 9	ENSP00000341351.5	Q96JK2-1
	DCAF5	ENST00000557386.5	TSL:1	c.2792A>C	p.Glu931Ala	missense	Exon 9 of 9	ENSP00000451845.1	Q96JK2-3
	DCAF5	ENST00000554215.5	TSL:1	c.2549A>C	p.Glu850Ala	missense	Exon 9 of 9	ENSP00000451551.1	Q96JK2-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248686 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458156 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725254

African (AFR) AF: 0.00 AC: 0 AN: 33258

American (AMR) AF: 0.00 AC: 0 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000586 AC: 5 AN: 85326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4834

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111338

Other (OTH) AF: 0.00 AC: 0 AN: 60188

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.028
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Polyphen		0.31	B
Vest4		0.18
MutPred		0.090		Loss of solvent accessibility (P = 0.0769)
MVP		0.30
MPC		0.81
ClinPred		0.52	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.047
Mutation Taster		=87/13	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

dbSNP: rs754319970; hg19: chr14-69520608;