chr4-41982694-C-T

Position:

• chr4-41982694-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029955.4(DCAF4L1):​c.902C>T​(p.Ala301Val) 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. 15/21 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: -0.609

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026709616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF4L1	NM_001029955.4	c.902C>T	p.Ala301Val	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.902C>T	p.Ala301Val	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

Apr 20, 2023

The c.902C>T (p.A301V) alteration is located in exon 1 (coding exon 1) of the DCAF4L1 gene. This alteration results from a C to T substitution at nucleotide position 902, causing the alanine (A) at amino acid position 301 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.77	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.025
Sift	Benign	0.73	T
Sift4G	Benign	1.0	T
Polyphen		0.11	B
Vest4		0.038
MutPred		0.36		Loss of sheet (P = 0.0817);
MVP		0.093
MPC		0.85
ClinPred		0.036	T
GERP RS		0.97
Varity_R		0.037
gMVP		0.17

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: chr4-41984711;