9-37801221-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024345.5(DCAF10):​c.355C>T​(p.Pro119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

DCAF10
NM_024345.5 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0700
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15323073).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCAF10NM_024345.5 linkc.355C>T p.Pro119Ser 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.355C>T p.Pro119Ser missense_variant Exon 1 of 7 1 NM_024345.5 ENSP00000366953.3 Q5QP82-1
ENSG00000255872ENST00000540557.1 linkn.*761-17158G>A intron_variant Intron 8 of 11 5 ENSP00000457548.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.06e-7
AC:
1
AN:
1415700
Hom.:
0
Cov.:
33
AF XY:
0.00000143
AC XY:
1
AN XY:
701196
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:
0.00
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.355C>T (p.P119S) 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 355, causing the proline (P) at amino acid position 119 to be replaced by a serine (S). 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
0.073
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.51
T
M_CAP
Pathogenic
0.86
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.97
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.53
N
REVEL
Benign
0.055
Sift
Benign
0.11
T
Sift4G
Benign
0.44
T
Polyphen
0.46
P
Vest4
0.071
MutPred
0.28
Gain of phosphorylation at P119 (P = 0.0287);
MVP
0.22
MPC
1.6
ClinPred
0.21
T
GERP RS
3.4
Varity_R
0.064
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-37801218; API