Genetic Variant NM_022156.5:c.953G>A (chr17-82060770-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022156.5(DUS1L):c.953G>A(p.Arg318Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,460,262 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: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DUS1L
NM_022156.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Publications

0 publications found

Variant links:

Genes affected

DUS1L (HGNC:30086): (dihydrouridine synthase 1 like) Predicted to enable tRNA dihydrouridine synthase activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

DUS1L links:

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ACMG classification

Classification was made for transcript

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=0.0745216).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022156.5. 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
	DUS1L	NM_022156.5	MANE Select	c.953G>A	p.Arg318Lys	missense	Exon 10 of 14	NP_071439.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUS1L	ENST00000306796.10	TSL:1 MANE Select	c.953G>A	p.Arg318Lys	missense	Exon 10 of 14	ENSP00000303515.5	Q6P1R4
DUS1L	ENST00000354321.11	TSL:1	c.953G>A	p.Arg318Lys	missense	Exon 9 of 13	ENSP00000346280.7	Q6P1R4
DUS1L	ENST00000538833.6	TSL:1	c.554G>A	p.Arg185Lys	missense	Exon 6 of 10	ENSP00000445110.2	H0YGW8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247526

AF XY:

0.00000744

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460262

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111716

Other (OTH)

AF:

0.0000166

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.015

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.34

M_CAP

Benign

0.011

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.41

PhyloP100

1.7

PrimateAI

Benign

0.32

PROVEAN

Benign

0.48

REVEL

Benign

0.077

Sift

Benign

1.0

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.15

MutPred

0.52

Gain of ubiquitination at R318 (P = 0.0185)

MVP

0.23

MPC

0.13

ClinPred

0.071

GERP RS

2.2

PromoterAI

0.0026

Neutral

(source)

Varity_R

0.088

gMVP

0.12

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over