Genetic Variant NM_022156.5:c.1249A>C (chr17-82058374-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022156.5(DUS1L):c.1249A>C(p.Lys417Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000503 in 1,489,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

DUS1L
NM_022156.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10073498).

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.1249A>C	p.Lys417Gln	missense	Exon 13 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.1249A>C	p.Lys417Gln	missense	Exon 13 of 14	ENSP00000303515.5	Q6P1R4
DUS1L	ENST00000354321.11	TSL:1	c.1249A>C	p.Lys417Gln	missense	Exon 12 of 13	ENSP00000346280.7	Q6P1R4
DUS1L	ENST00000538833.6	TSL:1	c.842A>C	p.Glu281Ala	missense	Exon 9 of 10	ENSP00000445110.2	H0YGW8

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000478

GnomAD2 exomes

AF:

0.000101

AC:

AN:

168478

AF XY:

0.0000673

show subpopulations

Gnomad AFR exome

AF:

0.000745

Gnomad AMR exome

AF:

0.000265

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:

0.000269

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1337620

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

652888

show subpopulations

African (AFR)

AF:

0.000812

AC:

AN:

29548

American (AMR)

AF:

0.000146

AC:

AN:

27324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19394

East Asian (EAS)

AF:

0.0000805

AC:

AN:

37246

South Asian (SAS)

AF:

0.0000150

AC:

AN:

66838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1049294

Other (OTH)

AF:

0.0000182

AC:

AN:

54808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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

AF:

0.000263

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41574

American (AMR)

AF:

0.000196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000101

AC:

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

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.037

Eigen

Benign

-0.074

Eigen_PC

Benign

0.026

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.077

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

6.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.62

REVEL

Benign

0.16

Sift

Benign

0.56

Sift4G

Benign

0.60

Polyphen

0.078

Vest4

0.59

MVP

0.40

MPC

0.18

ClinPred

0.099

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.45

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over