Variant chr1-167974842-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001198956.2(DCAF6):c.265A>G(p.Ile89Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000202 in 1,532,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

DCAF6
NM_001198956.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

DCAF6 links:

DCAF6 (HGNC:):

DCAF6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25238472).

BS2

High AC in GnomAdExome4 at 30 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF6	NM_001198956.2 linkuse as main transcript	c.265A>G	p.Ile89Val	missense_variant	4/22	ENST00000367840.4	NP_001185885.1	Q58WW2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4 linkuse as main transcript	c.265A>G	p.Ile89Val	missense_variant	4/22	1	NM_001198956.2	ENSP00000356814.3		Q58WW2-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000577

AC:

AN:

208050

Hom.:

AF XY:

0.0000530

AC XY:

AN XY:

113240

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:

0.000502

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000993

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

1380758

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

682456

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:

0.000389

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

May 20, 2024

The c.265A>G (p.I89V) alteration is located in exon 4 (coding exon 4) of the DCAF6 gene. This alteration results from a A to G substitution at nucleotide position 265, causing the isoleucine (I) at amino acid position 89 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

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.022

.;.;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

D;T;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.7

.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.095

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.60, 1.0, 0.95

.;P;D;P

Vest4

0.41

MutPred

0.41

.;Gain of methylation at R90 (P = 0.0435);Gain of methylation at R90 (P = 0.0435);Gain of methylation at R90 (P = 0.0435);

MVP

0.51

MPC

0.30

ClinPred

0.27

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over