chr14-69054450-C-A

Position:

• chr14-69054450-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003861.3(DCAF5):​c.2236G>T​(p.Gly746Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCAF5 NM_003861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.883

Genes affected

DCAF5 (HGNC:20224): (DDB1 and CUL4 associated factor 5) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15553981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF5	NM_003861.3	c.2236G>T	p.Gly746Cys	missense_variant	9/9	ENST00000341516.10	NP_003852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF5	ENST00000341516.10	c.2236G>T	p.Gly746Cys	missense_variant	9/9	1	NM_003861.3	ENSP00000341351.5
DCAF5	ENST00000557386.5	c.2233G>T	p.Gly745Cys	missense_variant	9/9	1		ENSP00000451845.1
DCAF5	ENST00000554215.5	c.1990G>T	p.Gly664Cys	missense_variant	9/9	1		ENSP00000451551.1
DCAF5	ENST00000556847.5	c.1990G>T	p.Gly664Cys	missense_variant	9/9	5		ENSP00000452052.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.2236G>T (p.G746C) alteration is located in exon 9 (coding exon 9) of the DCAF5 gene. This alteration results from a G to T substitution at nucleotide position 2236, causing the glycine (G) at amino acid position 746 to be replaced by a cysteine (C). 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	0.084
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.042	T;.;.;.
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.62	T;.;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.053	T;T;T;T
Sift4G	Uncertain	0.060	T;T;T;T
Polyphen		0.83	P;.;.;.
Vest4		0.21
MutPred		0.28		Loss of relative solvent accessibility (P = 0.0071);.;.;.;
MVP		0.25
MPC		0.23
ClinPred		0.40	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.048

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: chr14-69521167;