chr1-167993414-C-T

Variant names:

• chr1-167993414-C-T
• rs764787359
• NM_001198956.2:c.877C>T

Variant summary

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

The NM_001198956.2(DCAF6):​c.877C>T​(p.Pro293Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCAF6 NM_001198956.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• Publications: 1 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF6	NM_001198956.2	MANE Select	c.877C>T	p.Pro293Ser	missense	Exon 7 of 22	NP_001185885.1	Q58WW2-3
	DCAF6	NM_001349773.2		c.877C>T	p.Pro293Ser	missense	Exon 7 of 21	NP_001336702.1
	DCAF6	NM_001198957.2		c.784C>T	p.Pro262Ser	missense	Exon 6 of 21	NP_001185886.1	Q58WW2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF6	ENST00000367840.4	TSL:1 MANE Select	c.877C>T	p.Pro293Ser	missense	Exon 7 of 22	ENSP00000356814.3	Q58WW2-3
	DCAF6	ENST00000312263.10	TSL:1	c.877C>T	p.Pro293Ser	missense	Exon 7 of 19	ENSP00000311949.6	Q58WW2-1
	DCAF6	ENST00000856062.1		c.877C>T	p.Pro293Ser	missense	Exon 7 of 22	ENSP00000526121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250346 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461574 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.49
Sift	Benign	0.076	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.24		Gain of phosphorylation at P293 (P = 0.0062)
MVP		0.43
MPC		1.1
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.22
gMVP		0.59
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs764787359; hg19: chr1-167962652; COSMIC: COSV56578501; COSMIC: COSV56578501;