1-167993414-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001198956.2(DCAF6):​c.877C>A​(p.Pro293Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P293S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCAF6 NM_001198956.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCAF6	NM_001198956.2	c.877C>A	p.Pro293Thr	missense_variant	Exon 7 of 22	ENST00000367840.4	NP_001185885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCAF6	ENST00000367840.4	c.877C>A	p.Pro293Thr	missense_variant	Exon 7 of 22	1	NM_001198956.2	ENSP00000356814.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	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	0.96	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.1	.;M;M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Uncertain	0.55
Sift	Benign	0.047	D;D;T;T
Sift4G	Benign	0.062	T;T;T;D
Polyphen		1.0	.;D;D;D
Vest4		0.54
MutPred		0.23		.;Gain of phosphorylation at P293 (P = 0.0323);Gain of phosphorylation at P293 (P = 0.0323);Gain of phosphorylation at P293 (P = 0.0323);
MVP		0.50
MPC		1.2
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.32
gMVP		0.58

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

Other links and lift over

dbSNP: rs764787359; hg19: chr1-167962652;