chr14-69053935-A-T

Position:

• chr14-69053935-A-T

Variant summary

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

The NM_003861.3(DCAF5):​c.2751T>A​(p.Ser917Arg) 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. 14/21 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: 1.25

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=0.11209142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF5	NM_003861.3	c.2751T>A	p.Ser917Arg	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.2751T>A	p.Ser917Arg	missense_variant	9/9	1	NM_003861.3	ENSP00000341351.5
DCAF5	ENST00000557386.5	c.2748T>A	p.Ser916Arg	missense_variant	9/9	1		ENSP00000451845.1
DCAF5	ENST00000554215.5	c.2505T>A	p.Ser835Arg	missense_variant	9/9	1		ENSP00000451551.1
DCAF5	ENST00000556847.5	c.2505T>A	p.Ser835Arg	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

Jan 03, 2024

The c.2751T>A (p.S917R) alteration is located in exon 9 (coding exon 9) of the DCAF5 gene. This alteration results from a T to A substitution at nucleotide position 2751, causing the serine (S) at amino acid position 917 to be replaced by an arginine (R). 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	0.21
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.77	T;.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.058	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.26
MutPred		0.30		Gain of solvent accessibility (P = 0.0014);.;.;.;
MVP		0.40
MPC		0.39
ClinPred		0.42	T
GERP RS		2.8
Varity_R		0.13
gMVP		0.10

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: chr14-69520652;