Genetic Variant NM_001198956.2:c.472C>T (chr1-167987528-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001198956.2(DCAF6):c.472C>T(p.Leu158Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L158V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DCAF6
NM_001198956.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198956.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCAF6	NM_001198956.2	MANE Select	c.472C>T	p.Leu158Phe	missense	Exon 5 of 22	NP_001185885.1	Q58WW2-3
DCAF6	NM_001349773.2		c.472C>T	p.Leu158Phe	missense	Exon 5 of 21	NP_001336702.1
DCAF6	NM_001198957.2		c.379C>T	p.Leu127Phe	missense	Exon 4 of 21	NP_001185886.1	Q58WW2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCAF6	ENST00000367840.4	TSL:1 MANE Select	c.472C>T	p.Leu158Phe	missense	Exon 5 of 22	ENSP00000356814.3	Q58WW2-3
DCAF6	ENST00000312263.10	TSL:1	c.472C>T	p.Leu158Phe	missense	Exon 5 of 19	ENSP00000311949.6	Q58WW2-1
DCAF6	ENST00000856062.1		c.472C>T	p.Leu158Phe	missense	Exon 5 of 22	ENSP00000526121.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33268

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

85732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4432

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105164

Other (OTH)

AF:

0.00

AC:

AN:

59926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.1

PhyloP100

2.8

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.64

Sift

Benign

0.053

Sift4G

Benign

0.082

Polyphen

1.0

Vest4

0.80

MutPred

0.42

Gain of phosphorylation at T156 (P = 0.164)

MVP

0.84

MPC

1.2

ClinPred

0.99

GERP RS

5.1

Varity_R

0.40

gMVP

0.50

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over