rs587777425

chr1-160237145-G-Achr1-160237145-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2 PP5

The NM_015726.4(DCAF8):c.949C>T(p.Arg317Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,566,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: DCAF8 NM_015726.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.41

Genes affected

DCAF8 (HGNC:24891): (DDB1 and CUL4 associated factor 8) This gene encodes a WD repeat-containing protein that interacts with the Cul4-Ddb1 E3 ligase macromolecular complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP2: Missense variant where missense usually causes diseases, DCAF8
• PP5: Variant 1-160237145-G-A is Pathogenic according to our data. Variant chr1-160237145-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 133348.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCAF8	NM_015726.4	c.949C>T	p.Arg317Cys	missense_variant	6/14	ENST00000368074.6
DCAF8	NR_028103.2	n.1482C>T		non_coding_transcript_exon_variant	6/14
DCAF8	NR_028104.2	n.1408C>T		non_coding_transcript_exon_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCAF8	ENST00000368074.6	c.949C>T	p.Arg317Cys	missense_variant	6/14	5	NM_015726.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000990 AC: 14 AN: 1413982 Hom.: 0 Cov.: 29 AF XY: 0.00000716 AC XY: 5 AN XY: 698594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000265

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: 0.0000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000840 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Giant axonal neuropathy 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 11, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	-0.037	T
MutationAssessor	Uncertain	2.3	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Pathogenic	0.88
Sift	Benign	0.049	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.11	B;B;B;.
Vest4		0.65
MVP		0.62
MPC		1.2
ClinPred		0.95	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs587777425; hg19: chr1-160206935;