Variant 1-160218877-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_015726.4(DCAF8):c.1532C>T(p.Ala511Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCAF8
NM_015726.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

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]

DCAF8 links:

DCAF8 (HGNC:):

DCAF8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DCAF8. . Gene score misZ 3.1538 (greater than the threshold 3.09). Trascript score misZ 4.3168 (greater than threshold 3.09). GenCC has associacion of gene with giant axonal neuropathy 2.

BP4

Computational evidence support a benign effect (MetaRNN=0.07553145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF8	NM_015726.4 linkuse as main transcript	c.1532C>T	p.Ala511Val	missense_variant	12/14	ENST00000368074.6	NP_056541.2	Q5TAQ9-1B7Z8C9
DCAF8	NR_028103.2 linkuse as main transcript	n.2065C>T		non_coding_transcript_exon_variant	12/14
DCAF8	NR_028104.2 linkuse as main transcript	n.1991C>T		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF8	ENST00000368074.6 linkuse as main transcript	c.1532C>T	p.Ala511Val	missense_variant	12/14	5	NM_015726.4	ENSP00000357053.1		Q5TAQ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.1532C>T (p.A511V) alteration is located in exon 12 (coding exon 10) of the DCAF8 gene. This alteration results from a C to T substitution at nucleotide position 1532, causing the alanine (A) at amino acid position 511 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.58

.;.;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.075

B;B;B;.

Vest4

0.11

MutPred

0.31

.;.;.;Loss of disorder (P = 0.0796);

MVP

0.23

MPC

0.88

ClinPred

0.82

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over