14-69054057-T-G

Variant summary

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

The NM_003861.3(DCAF5):ā€‹c.2629A>Cā€‹(p.Thr877Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DCAF5
NM_003861.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.375
Variant links:
Genes affected
DCAF5 (HGNC:20224): (DDB1 and CUL4 associated factor 5) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.081323326).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DCAF5NM_003861.3 linkc.2629A>C p.Thr877Pro missense_variant 9/9 ENST00000341516.10 NP_003852.1 Q96JK2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DCAF5ENST00000341516.10 linkc.2629A>C p.Thr877Pro missense_variant 9/91 NM_003861.3 ENSP00000341351.5 Q96JK2-1
DCAF5ENST00000557386.5 linkc.2626A>C p.Thr876Pro missense_variant 9/91 ENSP00000451845.1 Q96JK2-3
DCAF5ENST00000554215.5 linkc.2383A>C p.Thr795Pro missense_variant 9/91 ENSP00000451551.1 Q96JK2-2
DCAF5ENST00000556847.5 linkc.2383A>C p.Thr795Pro missense_variant 9/95 ENSP00000452052.1 Q96JK2-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461724
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2022The c.2629A>C (p.T877P) alteration is located in exon 9 (coding exon 9) of the DCAF5 gene. This alteration results from a A to C substitution at nucleotide position 2629, causing the threonine (T) at amino acid position 877 to be replaced by a proline (P). 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
0.067
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.027
T;.;.;.
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.45
T;.;T;T
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.081
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.81
L;.;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.75
N;N;N;N
REVEL
Benign
0.074
Sift
Benign
0.17
T;T;T;T
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.41
B;.;.;.
Vest4
0.11
MutPred
0.16
Loss of sheet (P = 0.003);.;.;.;
MVP
0.36
MPC
0.27
ClinPred
0.35
T
GERP RS
2.7
Varity_R
0.11
gMVP
0.078

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: rs2037852520; hg19: chr14-69520774; API