Variant 19-5785625-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020175.3(DUS3L):c.1729G>C(p.Glu577Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000746 in 1,608,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

DUS3L
NM_020175.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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:

DUS3L (HGNC:):

DUS3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS3L	NM_020175.3 linkuse as main transcript	c.1729G>C	p.Glu577Gln	missense_variant	11/13	ENST00000309061.12	NP_064560.2	Q96G46-1B2RDV7
DUS3L	NM_001161619.2 linkuse as main transcript	c.1003G>C	p.Glu335Gln	missense_variant	10/12		NP_001155091.1	Q96G46-3
DUS3L	XM_017027020.2 linkuse as main transcript	c.1687G>C	p.Glu563Gln	missense_variant	10/12		XP_016882509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUS3L	ENST00000309061.12 linkuse as main transcript	c.1729G>C	p.Glu577Gln	missense_variant	11/13	1	NM_020175.3	ENSP00000311977.5		Q96G46-1
ENSG00000267157	ENST00000586012.1 linkuse as main transcript	c.-6G>C		upstream_gene_variant		3		ENSP00000466514.1		K7EMI3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152236

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243110

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1456374

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jul 19, 2023

The c.1729G>C (p.E577Q) alteration is located in exon 11 (coding exon 11) of the DUS3L gene. This alteration results from a G to C substitution at nucleotide position 1729, causing the glutamic acid (E) at amino acid position 577 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.5

.;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.044

D;T

Polyphen

0.97

D;P

Vest4

0.44

MutPred

0.59

.;Gain of MoRF binding (P = 0.0215);

MVP

0.49

MPC

1.2

ClinPred

0.95

GERP RS

3.4

Varity_R

0.42

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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