Variant 1-160231312-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_015726.4(DCAF8):c.1055G>A(p.Arg352Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DCAF8
NM_015726.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.43

Variant links:

Genes affected

DCAF8 (HGNC:24891): (DDB1 and CUL4 associated factor 8) This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

DCAF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DCAF8. . Gene score misZ 3.1538 (greater than the threshold 3.09). Trascript score misZ 4.3168 (greater than threshold 3.09). GenCC has associacion of gene with giant axonal neuropathy 2.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCAF8	NM_015726.4 linkuse as main transcript	c.1055G>A	p.Arg352Gln	missense_variant	7/14	ENST00000368074.6
DCAF8	NR_028103.2 linkuse as main transcript	n.1588G>A		non_coding_transcript_exon_variant	7/14
DCAF8	NR_028104.2 linkuse as main transcript	n.1514G>A		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCAF8	ENST00000368074.6 linkuse as main transcript	c.1055G>A	p.Arg352Gln	missense_variant	7/14	5	NM_015726.4	P1	Q5TAQ9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251378

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135866

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461268

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726994

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;T;T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.9

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.57

P;P;P;.

Vest4

0.61

MutPred

0.55

.;.;.;Loss of catalytic residue at R506 (P = 0.1881);

MVP

0.49

MPC

1.0

ClinPred

0.89

GERP RS

4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.16

gMVP

0.71

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over