Variant chr19-5785476-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020175.3(DUS3L):c.1787A>C(p.Gln596Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000561 in 1,425,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

DUS3L
NM_020175.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33421195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS3L	NM_020175.3 linkuse as main transcript	c.1787A>C	p.Gln596Pro	missense_variant	12/13	ENST00000309061.12	NP_064560.2	Q96G46-1B2RDV7
DUS3L	NM_001161619.2 linkuse as main transcript	c.1061A>C	p.Gln354Pro	missense_variant	11/12		NP_001155091.1	Q96G46-3
DUS3L	XM_017027020.2 linkuse as main transcript	c.1745A>C	p.Gln582Pro	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.1787A>C	p.Gln596Pro	missense_variant	12/13	1	NM_020175.3	ENSP00000311977.5		Q96G46-1
ENSG00000267157	ENST00000586012.1 linkuse as main transcript	c.53A>C	p.Gln18Pro	missense_variant	2/3	3		ENSP00000466514.1		K7EMI3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000338

AC:

AN:

207116

Hom.:

AF XY:

0.0000264

AC XY:

AN XY:

113496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000236

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000561

AC:

AN:

1425216

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

705308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000198

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000334

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

Nov 20, 2024

The c.1787A>C (p.Q596P) alteration is located in exon 12 (coding exon 12) of the DUS3L gene. This alteration results from a A to C substitution at nucleotide position 1787, causing the glutamine (Q) at amino acid position 596 to be replaced by a proline (P). 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

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

.;.;L

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.5

.;D;D

REVEL

Benign

0.20

Sift

Benign

0.052

.;T;D

Sift4G

Uncertain

0.040

D;T;T

Polyphen

0.039, 0.0040

.;B;B

Vest4

0.65

MutPred

0.62

.;.;Gain of catalytic residue at P595 (P = 0.0112);

MVP

0.25

MPC

1.0

ClinPred

0.39

GERP RS

3.6

Varity_R

0.93

gMVP

0.93

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