NM_025230.5:c.376G>C

Variant names:

• chr14-24117358-G-C
• rs61744791
• NM_025230.5:c.376G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025230.5(DCAF11):​c.376G>C​(p.Ala126Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A126T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCAF11 NM_025230.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06359604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF11	NM_025230.5	c.376G>C	p.Ala126Pro	missense_variant	Exon 4 of 15	ENST00000446197.8	NP_079506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF11	ENST00000446197.8	c.376G>C	p.Ala126Pro	missense_variant	Exon 4 of 15	1	NM_025230.5	ENSP00000415556.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T;.;T;T;T;.;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.064	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;N;.;.;.;.;.;.
PhyloP100		0.58
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.91	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.17	T;T;T;D;D;D;D;D;T
Sift4G	Benign	0.28	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.47
MutPred		0.48		Gain of disorder (P = 0.0589);.;Gain of disorder (P = 0.0589);.;.;.;Gain of disorder (P = 0.0589);Gain of disorder (P = 0.0589);.;
MVP		0.12
MPC		0.46
ClinPred		0.17	T
GERP RS		0.62
Varity_R		0.044
gMVP		0.52
Mutation Taster		=94/6	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

dbSNP: rs61744791; hg19: chr14-24586567;