9-34125241-G-C

Position:

• chr9-34125241-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015397.4(DCAF12):​c.115C>G​(p.Leu39Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCAF12 NM_015397.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39

Genes affected

DCAF12 (HGNC:19911): (DDB1 and CUL4 associated factor 12) 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. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18312606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCAF12	NM_015397.4	c.115C>G	p.Leu39Val	missense_variant	2/9	ENST00000361264.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCAF12	ENST00000361264.9	c.115C>G	p.Leu39Val	missense_variant	2/9	1	NM_015397.4	P1
DCAF12	ENST00000396990.6	c.61C>G	p.Leu21Val	missense_variant	2/5	3
DCAF12	ENST00000450964.1	c.52C>G	p.Leu18Val	missense_variant	2/5	5
DCAF12	ENST00000463286.1	n.259C>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.115C>G (p.L39V) alteration is located in exon 2 (coding exon 2) of the DCAF12 gene. This alteration results from a C to G substitution at nucleotide position 115, causing the leucine (L) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0033	T;T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.29	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.42	T;T;.
Polyphen		0.0070	B;.;.
Vest4		0.48
MutPred		0.21		Gain of methylation at K35 (P = 0.0652);.;.;
MVP		0.52
MPC		0.45
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34125239;