Genetic Variant DCAF10:p.Arg130Cys (chr9-37801254-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_024345.5(DCAF10):c.388C>T(p.Arg130Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000209 in 1,436,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCAF10
NM_024345.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

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]

DCAF10 links:

ENSG00000255872 (HGNC:):

ENSG00000255872 links:

EXOSC3 (HGNC:17944): (exosome component 3) This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

EXOSC3 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
DCAF10	NM_024345.5 link	c.388C>T	p.Arg130Cys	missense_variant	Exon 1 of 7	ENST00000377724.8	NP_077321.3	Q5QP82-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF10	ENST00000377724.8 link	c.388C>T	p.Arg130Cys	missense_variant	Exon 1 of 7	1	NM_024345.5	ENSP00000366953.3		Q5QP82-1
ENSG00000255872	ENST00000540557.1 link	n.*761-17191G>A		intron_variant	Intron 8 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1436688

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713498

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.388C>T (p.R130C) alteration is located in exon 1 (coding exon 1) of the DCAF10 gene. This alteration results from a C to T substitution at nucleotide position 388, causing the arginine (R) at amino acid position 130 to be replaced by a cysteine (C). 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

0.83

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.94

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.97

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.016

Vest4

0.65

MutPred

0.52

Loss of MoRF binding (P = 0.0031);

MVP

0.35

MPC

2.3

ClinPred

0.99

GERP RS

3.5

Varity_R

0.79

gMVP

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over