chr1-167936982-C-T

Variant names:

• chr1-167936982-C-T
• rs1225719696
• NM_001198956.2:c.71C>T

Variant summary

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

The NM_001349777.2(DCAF6):​c.-309C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-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: 31)
• Consequence: DCAF6 NM_001349777.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• Publications: 0 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]

MPC2 (HGNC:24515): (mitochondrial pyruvate carrier 2) Enables identical protein binding activity. Predicted to be involved in mitochondrial pyruvate transmembrane transport. Predicted to act upstream of or within mitochondrial acetyl-CoA biosynthetic process from pyruvate and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MPC2 Gene-Disease associations (from GenCC):

• metabolic disease

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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_001349777.2. 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.71C>T	p.Pro24Leu	missense	Exon 1 of 22	NP_001185885.1	Q58WW2-3
	MPC2	NM_001143674.4	MANE Select	c.-101G>A		5_prime_UTR	Exon 1 of 6	NP_001137146.1	O95563
	DCAF6	NM_001349777.2		c.-309C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001336706.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF6	ENST00000367840.4	TSL:1 MANE Select	c.71C>T	p.Pro24Leu	missense	Exon 1 of 22	ENSP00000356814.3	Q58WW2-3
	DCAF6	ENST00000312263.10	TSL:1	c.71C>T	p.Pro24Leu	missense	Exon 1 of 19	ENSP00000311949.6	Q58WW2-1
	MPC2	ENST00000271373.9	TSL:1 MANE Select	c.-101G>A		5_prime_UTR	Exon 1 of 6	ENSP00000271373.4	O95563

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.062	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.28		Loss of sheet (P = 7e-04)
MVP		0.58
MPC		1.1
ClinPred		1.0	D
GERP RS		3.4
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.40
gMVP		0.51
Mutation Taster		=73/27	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: rs1225719696; hg19: chr1-167906220;