dbSNP rs762607568: DUS3L:p.Ala648Val (chr19-5785213-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_020175.3(DUS3L):c.1943C>T(p.Ala648Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,607,748 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A648E) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

DUS3L
NM_020175.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37862074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS3L	NM_020175.3 link	c.1943C>T	p.Ala648Val	missense_variant	Exon 13 of 13	ENST00000309061.12	NP_064560.2	Q96G46-1B2RDV7
DUS3L	NM_001161619.2 link	c.1217C>T	p.Ala406Val	missense_variant	Exon 12 of 12		NP_001155091.1	Q96G46-3
DUS3L	XM_017027020.2 link	c.1901C>T	p.Ala634Val	missense_variant	Exon 12 of 12		XP_016882509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUS3L	ENST00000309061.12 link	c.1943C>T	p.Ala648Val	missense_variant	Exon 13 of 13	1	NM_020175.3	ENSP00000311977.5		Q96G46-1
ENSG00000267157	ENST00000586012.1 link	c.146+170C>T		intron_variant	Intron 2 of 2	3		ENSP00000466514.1		K7EMI3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000336

AC:

AN:

238184

Hom.:

AF XY:

0.0000463

AC XY:

AN XY:

129656

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:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1455538

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

723592

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:

0.000317

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.7

.;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;P

Vest4

0.36

MutPred

0.16

.;Gain of methylation at K650 (P = 0.0528);

MVP

0.72

MPC

1.1

ClinPred

0.76

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.71

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over