NM_024345.5:c.199C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024345.5(DCAF10):c.199C>T(p.Arg67Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,379,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.000014 ( 0 hom. )

Consequence

DCAF10
NM_024345.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23313114).

BS2

High AC in GnomAdExome4 at 19 AD gene.

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.199C>T	p.Arg67Cys	missense	Exon 1 of 7	NP_077321.3
	DCAF10	NM_001286810.2		c.20+418C>T		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.199C>T	p.Arg67Cys	missense	Exon 1 of 7	ENSP00000366953.3	Q5QP82-1
DCAF10	ENST00000242323.8	TSL:1	c.20+418C>T		intron	N/A	ENSP00000242323.8	A0A0A0MQT4
ENSG00000255872	ENST00000540557.1	TSL:5	n.*761-17002G>A		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000233

AC:

AN:

128600

AF XY:

0.0000140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000589

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1379894

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

681874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28974

American (AMR)

AF:

0.00

AC:

AN:

36590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24506

East Asian (EAS)

AF:

0.00

AC:

AN:

33934

South Asian (SAS)

AF:

0.00

AC:

AN:

78286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

1079376

Other (OTH)

AF:

0.0000174

AC:

AN:

57434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

0.12

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.39

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.031

Polyphen

0.98

Vest4

0.091

MutPred

0.35

Gain of catalytic residue at P66 (P = 0.0073)

MVP

0.15

MPC

2.0

ClinPred

0.65

GERP RS

-0.57

PromoterAI

0.0013

Neutral

(source)

Varity_R

0.12

gMVP

0.32

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over