14-24118071-C-G

Variant names:

• chr14-24118071-C-G
• rs371242058
• NM_025230.5:c.493C>G

Variant summary

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

The NM_025230.5(DCAF11):​c.493C>G​(p.Leu165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,611,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DCAF11 NM_025230.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 1 publications found

Genes affected

DCAF11 (HGNC:20258): (DDB1 and CUL4 associated factor 11) This gene encodes a WD repeat-containing protein that interacts with the COP9 signalosome, a macromolecular complex that interacts with cullin-RING E3 ligases and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

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=0.06924859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025230.5. 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
	DCAF11	NM_025230.5	MANE Select	c.493C>G	p.Leu165Val	missense	Exon 6 of 15	NP_079506.3
	DCAF11	NM_001163484.2		c.493C>G	p.Leu165Val	missense	Exon 6 of 15	NP_001156956.1	Q8TEB1-1
	DCAF11	NM_181357.2		c.415C>G	p.Leu139Val	missense	Exon 6 of 15	NP_852002.1	Q59GN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF11	ENST00000446197.8	TSL:1 MANE Select	c.493C>G	p.Leu165Val	missense	Exon 6 of 15	ENSP00000415556.4	Q8TEB1-1
	DCAF11	ENST00000559115.5	TSL:1	c.493C>G	p.Leu165Val	missense	Exon 6 of 15	ENSP00000452898.1	Q8TEB1-1
	DCAF11	ENST00000396936.5	TSL:1	c.193C>G	p.Leu65Val	missense	Exon 4 of 13	ENSP00000380142.1	Q8TEB1-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1459058 Hom.: 0 Cov.: 32 AF XY: 0.00000827 AC XY: 6 AN XY: 725882

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111038

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 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	0.072
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		1.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.093
Sift	Benign	0.60	T
Sift4G	Benign	0.51	T
Polyphen		0.0050	B
Vest4		0.17
MVP		0.39
MPC		0.36
ClinPred		0.16	T
GERP RS		2.4
Varity_R		0.046
gMVP		0.21
Mutation Taster		=94/6	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: rs371242058; hg19: chr14-24587280;