9-37801207-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024345.5(DCAF10):​c.341C>T​(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,553,430 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000089 ( 1 hom. )

Consequence

DCAF10
NM_024345.5 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.610
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.054770768).
BS2
High AC in GnomAdExome4 at 125 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCAF10NM_024345.5 linkc.341C>T p.Ala114Val 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
DCAF10ENST00000377724.8 linkc.341C>T p.Ala114Val missense_variant Exon 1 of 7 1 NM_024345.5 ENSP00000366953.3 Q5QP82-1
ENSG00000255872ENST00000540557.1 linkn.*761-17144G>A intron_variant Intron 8 of 11 5 ENSP00000457548.1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000141
AC:
21
AN:
149084
Hom.:
0
AF XY:
0.000206
AC XY:
17
AN XY:
82592
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 SAS exome
AF:
0.000759
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000684
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000892
AC:
125
AN:
1401296
Hom.:
1
Cov.:
33
AF XY:
0.000115
AC XY:
80
AN XY:
692884
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:
0.000682
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000599
Gnomad4 OTH exome
AF:
0.0000518
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000682
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000891
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.341C>T (p.A114V) 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 341, causing the alanine (A) at amino acid position 114 to be replaced by a valine (V). 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
0.088
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.50
T
M_CAP
Pathogenic
0.72
D
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.42
N
REVEL
Benign
0.12
Sift
Benign
0.10
T
Sift4G
Uncertain
0.028
D
Polyphen
0.0
B
Vest4
0.12
MutPred
0.18
Loss of methylation at R109 (P = 0.0933);
MVP
0.33
MPC
1.4
ClinPred
0.080
T
GERP RS
1.7
Varity_R
0.034
gMVP
0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745311749; hg19: chr9-37801204; COSMIC: COSV54290270; COSMIC: COSV54290270; API