Variant 14-72945918-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015604.4(DCAF4):c.569A>C(p.Asn190Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,614,194 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

DCAF4
NM_015604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.07

Variant links:

Genes affected

DCAF4 (HGNC:20229): (DDB1 and CUL4 associated factor 4) 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]

DCAF4 links:

DCAF4 (HGNC:):

DCAF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09442541).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4	NM_015604.4 linkuse as main transcript	c.569A>C	p.Asn190Thr	missense_variant	7/14	ENST00000358377.7	NP_056419.2	Q8WV16-1B2RDD6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF4	ENST00000358377.7 linkuse as main transcript	c.569A>C	p.Asn190Thr	missense_variant	7/14	1	NM_015604.4	ENSP00000351147.2		Q8WV16-1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000728

AC:

183

AN:

251478

Hom.:

AF XY:

0.000795

AC XY:

108

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00123

AC:

1791

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

858

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152302

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000759

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00174

EpiControl

AF:

0.00124

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 submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.569A>C (p.N190T) alteration is located in exon 7 (coding exon 6) of the DCAF4 gene. This alteration results from a A to C substitution at nucleotide position 569, causing the asparagine (N) at amino acid position 190 to be replaced by a threonine (T). 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

0.28

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

T;.;.;.;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.094

T;T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.7

M;.;.;.;M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

D;D;D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.020

D;D;D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D;D;D

Polyphen

0.97

D;D;.;.;.;.

Vest4

0.64

MVP

0.88

MPC

0.74

ClinPred

0.21

GERP RS

4.9

Varity_R

0.23

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over