4-41982552-C-A

Position:

• chr4-41982552-C-A

Variant summary

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

The NM_001029955.4(DCAF4L1):​c.760C>A​(p.Arg254Ser) 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. 12/21 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: DCAF4L1 NM_001029955.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

Genes affected

DCAF4L1 (HGNC:27723): (DDB1 and CUL4 associated factor 4 like 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33047307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4L1	NM_001029955.4	c.760C>A	p.Arg254Ser	missense_variant	1/1	ENST00000333141.7	NP_001025126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF4L1	ENST00000333141.7	c.760C>A	p.Arg254Ser	missense_variant	1/1	6	NM_001029955.4	ENSP00000327796.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

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

Jul 13, 2022

The c.760C>A (p.R254S) alteration is located in exon 1 (coding exon 1) of the DCAF4L1 gene. This alteration results from a C to A substitution at nucleotide position 760, causing the arginine (R) at amino acid position 254 to be replaced by a serine (S). 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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.034	B
Vest4		0.33
MutPred		0.74		Loss of methylation at R254 (P = 0.0189);
MVP		0.043
MPC		2.0
ClinPred		1.0	D
GERP RS		-0.066
Varity_R		0.75
gMVP		0.32

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: chr4-41984569;