chr19-5785485-C-T

Variant names:

• chr19-5785485-C-T
• rs369595939
• NM_020175.3:c.1778G>A

Variant summary

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

The NM_020175.3(DUS3L):​c.1778G>A​(p.Arg593Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,572,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: DUS3L NM_020175.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

Genes affected

DUS3L (HGNC:26920): (dihydrouridine synthase 3 like) Enables RNA binding activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267157 (HGNC:):

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=0.10672653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020175.3. 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
	DUS3L	NM_020175.3	MANE Select	c.1778G>A	p.Arg593Gln	missense	Exon 12 of 13	NP_064560.2	Q96G46-1
	DUS3L	NM_001161619.2		c.1052G>A	p.Arg351Gln	missense	Exon 11 of 12	NP_001155091.1	Q96G46-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS3L	ENST00000309061.12	TSL:1 MANE Select	c.1778G>A	p.Arg593Gln	missense	Exon 12 of 13	ENSP00000311977.5	Q96G46-1
	DUS3L	ENST00000320699.12	TSL:1	c.1052G>A	p.Arg351Gln	missense	Exon 11 of 12	ENSP00000315558.7	Q96G46-3
	ENSG00000267157	ENST00000586012.1	TSL:3	c.44G>A	p.Arg15Gln	missense	Exon 2 of 3	ENSP00000466514.1	K7EMI3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000196 AC: 4 AN: 203794 AF XY: 0.0000179

Gnomad AFR exome AF: 0.0000759

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000218

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000141 AC: 20 AN: 1420574 Hom.: 0 Cov.: 31 AF XY: 0.0000128 AC XY: 9 AN XY: 702430

African (AFR) AF: 0.0000307 AC: 1 AN: 32538

American (AMR) AF: 0.00 AC: 0 AN: 39908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.000136 AC: 11 AN: 80832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091206

Other (OTH) AF: 0.00 AC: 0 AN: 58458

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000605 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.000234 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.034
Sift	Benign	0.30	T
Sift4G	Benign	0.18	T
Polyphen		0.093	B
Vest4		0.17
MVP		0.12
MPC		0.51
ClinPred		0.061	T
GERP RS		-1.0
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.57
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369595939; hg19: chr19-5785496;