NM_001029955.4:c.1159C>G

Variant names:

• chr4-41982951-C-G
• rs199598081
• NM_001029955.4:c.1159C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001029955.4(DCAF4L1):​c.1159C>G​(p.Arg387Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R387W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCAF4L1 NM_001029955.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762
• Publications: 4 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08858895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF4L1	NM_001029955.4	MANE Select	c.1159C>G	p.Arg387Gly	missense	Exon 1 of 1	NP_001025126.2	Q3SXM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF4L1	ENST00000333141.7	TSL:6 MANE Select	c.1159C>G	p.Arg387Gly	missense	Exon 1 of 1	ENSP00000327796.5	Q3SXM0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248722 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460012 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726238

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.0000225 AC: 1 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111182

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.091	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	N
PhyloP100		0.76
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.035
Sift	Benign	0.40	T
Sift4G	Benign	0.25	T
Polyphen		0.40	B
Vest4		0.13
MutPred		0.45		Gain of glycosylation at Y391 (P = 0.0418)
MVP		0.093
MPC		1.1
ClinPred		0.086	T
GERP RS		-0.066
Varity_R		0.12
gMVP		0.76
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs199598081; hg19: chr4-41984968;