Variant chr19-5785485-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 15/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

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]

DUS3L links:

ENSG00000267157 (HGNC:):

ENSG00000267157 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10672653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS3L	NM_020175.3 linkuse as main transcript	c.1778G>A	p.Arg593Gln	missense_variant	12/13	ENST00000309061.12	NP_064560.2	Q96G46-1B2RDV7
DUS3L	NM_001161619.2 linkuse as main transcript	c.1052G>A	p.Arg351Gln	missense_variant	11/12		NP_001155091.1	Q96G46-3
DUS3L	XM_017027020.2 linkuse as main transcript	c.1736G>A	p.Arg579Gln	missense_variant	11/12		XP_016882509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUS3L	ENST00000309061.12 linkuse as main transcript	c.1778G>A	p.Arg593Gln	missense_variant	12/13	1	NM_020175.3	ENSP00000311977.5		Q96G46-1
ENSG00000267157	ENST00000586012.1 linkuse as main transcript	c.44G>A	p.Arg15Gln	missense_variant	2/3	3		ENSP00000466514.1		K7EMI3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000196

AC:

AN:

203794

Hom.:

AF XY:

0.0000179

AC XY:

AN XY:

111586

show subpopulations

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 SAS exome

AF:

0.0000412

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1420574

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

702430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000733

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1778G>A (p.R593Q) alteration is located in exon 12 (coding exon 12) of the DUS3L gene. This alteration results from a G to A substitution at nucleotide position 1778, causing the arginine (R) at amino acid position 593 to be replaced by a glutamine (Q). 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

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.037

.;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.034

Sift

Benign

0.30

.;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.093, 0.17

.;B;B

Vest4

0.17, 0.16

MVP

0.12

MPC

0.51

ClinPred

0.061

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over