1-160225101-C-A

Position:

• chr1-160225101-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_015726.4(DCAF8):​c.1162G>T​(p.Ala388Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,824 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCAF8 NM_015726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66

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 (HGNC:):

ACMG classification

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=0.21383688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF8	NM_015726.4	c.1162G>T	p.Ala388Ser	missense_variant	9/14	ENST00000368074.6	NP_056541.2
DCAF8	NR_028103.2	n.1695G>T		non_coding_transcript_exon_variant	9/14
DCAF8	NR_028104.2	n.1621G>T		non_coding_transcript_exon_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF8	ENST00000368074.6	c.1162G>T	p.Ala388Ser	missense_variant	9/14	5	NM_015726.4	ENSP00000357053.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

DCAF8: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;T;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	.;.;T;.
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.3	L;L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.014	D;D;D;T
Sift4G	Uncertain	0.060	T;T;T;T
Polyphen		0.36	B;B;B;.
Vest4		0.29
MutPred		0.45		.;.;.;Gain of disorder (P = 0.0289);
MVP		0.43
MPC		0.84
ClinPred		0.85	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-160194891;