chr9-37842103-G-A

Position:

• chr9-37842103-G-A

Variant summary

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

The NM_024345.5(DCAF10):​c.668G>A​(p.Arg223Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCAF10 NM_024345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57

Genes affected

DCAF10 (HGNC:23686): (DDB1 and CUL4 associated factor 10) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255872 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF10	NM_024345.5	c.668G>A	p.Arg223Gln	missense_variant	3/7	ENST00000377724.8	NP_077321.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF10	ENST00000377724.8	c.668G>A	p.Arg223Gln	missense_variant	3/7	1	NM_024345.5	ENSP00000366953.3
DCAF10	ENST00000242323.8	c.149G>A	p.Arg50Gln	missense_variant	3/7	1		ENSP00000242323.8
ENSG00000255872	ENST00000540557.1	n.*682-9962C>T		intron_variant		5		ENSP00000457548.1
DCAF10	ENST00000461549.1	n.109-12677G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Oct 03, 2024

The c.668G>A (p.R223Q) alteration is located in exon 3 (coding exon 3) of the DCAF10 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the arginine (R) at amino acid position 223 to be replaced by a glutamine (Q). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.49	N;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D;.
REVEL	Uncertain	0.39
Sift	Benign	0.14	T;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.54		Loss of stability (P = 0.2182);.;
MVP		0.56
MPC		2.2
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr9-37842100;