Genetic Variant DCAF10:p.Arg52Pro (chr9-37801021-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024345.5(DCAF10):c.155G>C(p.Arg52Pro) 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. 15/22 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. R52Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DCAF10
NM_024345.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 1B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EXOSC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13184601).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024345.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF10	NM_024345.5	MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 1 of 7	NP_077321.3
	DCAF10	NM_001286810.2		c.20+374G>C		intron	N/A	NP_001273739.1	A0A0A0MQT4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCAF10	ENST00000377724.8	TSL:1 MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 1 of 7	ENSP00000366953.3	Q5QP82-1
DCAF10	ENST00000242323.8	TSL:1	c.20+374G>C		intron	N/A	ENSP00000242323.8	A0A0A0MQT4
ENSG00000255872	ENST00000540557.1	TSL:5	n.*761-16958C>G		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1388496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687204

African (AFR)

AF:

0.00

AC:

AN:

29102

American (AMR)

AF:

0.00

AC:

AN:

38646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24362

East Asian (EAS)

AF:

0.00

AC:

AN:

34582

South Asian (SAS)

AF:

0.00

AC:

AN:

78828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4038

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085886

Other (OTH)

AF:

0.00

AC:

AN:

57728

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PhyloP100

1.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.54

REVEL

Benign

0.038

Sift

Benign

0.32

Sift4G

Benign

0.33

Polyphen

0.17

Vest4

0.18

MutPred

0.32

Gain of glycosylation at R52 (P = 0.0093)

MVP

0.15

MPC

1.8

ClinPred

0.33

GERP RS

2.4

PromoterAI

0.010

Neutral

(source)

Varity_R

0.20

gMVP

0.25

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over