4-41982244-A-G

Position:

• chr4-41982244-A-G

Variant summary

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

The NM_001029955.4(DCAF4L1):​c.452A>G​(p.Asp151Gly) 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: DCAF4L1 NM_001029955.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

Genes affected

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

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=0.116542995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4L1	NM_001029955.4	c.452A>G	p.Asp151Gly	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.452A>G	p.Asp151Gly	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

Jun 22, 2024

The c.452A>G (p.D151G) alteration is located in exon 1 (coding exon 1) of the DCAF4L1 gene. This alteration results from a A to G substitution at nucleotide position 452, causing the aspartic acid (D) at amino acid position 151 to be replaced by a glycine (G). 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	0.086
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.14	B
Vest4		0.085
MutPred		0.39		Loss of sheet (P = 0.0228);
MVP		0.28
MPC		1.1
ClinPred		0.52	D
GERP RS		0.69
Varity_R		0.18
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr4-41984261;