1-160217659-G-A

Position:

• chr1-160217659-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_015726.4(DCAF8):​c.1727C>T​(p.Ser576Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S576P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCAF8 NM_015726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.82

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 2 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=0.28436714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF8	NM_015726.4	c.1727C>T	p.Ser576Phe	missense_variant	14/14	ENST00000368074.6	NP_056541.2
DCAF8	NR_028103.2	n.2260C>T		non_coding_transcript_exon_variant	14/14
DCAF8	NR_028104.2	n.2186C>T		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF8	ENST00000368074.6	c.1727C>T	p.Ser576Phe	missense_variant	14/14	5	NM_015726.4	ENSP00000357053.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Giant axonal neuropathy 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Aug 30, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	.;.;T;.
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.017	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.99	D;D;D;.
Vest4		0.54
MutPred		0.28		.;.;.;Loss of phosphorylation at S730 (P = 0.001);
MVP		0.32
MPC		2.1
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.48

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: chr1-160187449;