chr3-51403261-A-G

Position:

• chr3-51403261-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001387579.1(DCAF1):​c.4347T>C​(p.Asp1449Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,798 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCAF1 NM_001387579.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.545

Genes affected

DCAF1 (HGNC:30911): (DDB1 and CUL4 associated factor 1) Enables estrogen receptor binding activity and histone kinase activity (H2A-T120 specific). Involved in cell competition in a multicellular organism; histone H2A-T120 phosphorylation; and negative regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. Part of Cul4-RING E3 ubiquitin ligase complex. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

DCAF1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 3-51403261-A-G is Benign according to our data. Variant chr3-51403261-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.545 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF1	NM_001387579.1	c.4347T>C	p.Asp1449Asp	synonymous_variant	24/25	ENST00000684031.1	NP_001374508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF1	ENST00000684031.1	c.4347T>C	p.Asp1449Asp	synonymous_variant	24/25		NM_001387579.1	ENSP00000506880.1
DCAF1	ENST00000504652.5	c.4344T>C	p.Asp1448Asp	synonymous_variant	23/25	1		ENSP00000421724.2
DCAF1	ENST00000423656.5	c.4347T>C	p.Asp1449Asp	synonymous_variant	23/25	5		ENSP00000393183.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460798 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726576

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

DCAF1: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.8
DANN	Benign	0.56
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-51440695;