chr9-34098464-T-C

Position:

• chr9-34098464-T-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.655A>G​(p.Lys219Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCAF12 NM_015397.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85

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=0.14466387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF12	NM_015397.4	c.655A>G	p.Lys219Glu	missense_variant	5/9	ENST00000361264.9	NP_056212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF12	ENST00000361264.9	c.655A>G	p.Lys219Glu	missense_variant	5/9	1	NM_015397.4	ENSP00000355114.3
DCAF12	ENST00000396990.6	c.601A>G	p.Lys201Glu	missense_variant	5/5	3		ENSP00000380187.2
DCAF12	ENST00000450964.1	c.*24A>G		downstream_gene_variant		5		ENSP00000415833.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 14, 2023

The c.655A>G (p.K219E) alteration is located in exon 5 (coding exon 5) of the DCAF12 gene. This alteration results from a A to G substitution at nucleotide position 655, causing the lysine (K) at amino acid position 219 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.0067	T;T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.081
Sift	Benign	0.95	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.21	B;.
Vest4		0.32
MutPred		0.32		Loss of ubiquitination at K219 (P = 0.0118);.;
MVP		0.60
MPC		0.63
ClinPred		0.37	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.28

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: chr9-34098462;