Genetic Variant DUT:c.280+9G>A (chr15-48331804-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001025248.2(DUT):c.280+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,365,836 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

DUT
NM_001025248.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.56

Publications

0 publications found

Variant links:

Genes affected

DUT (HGNC:3078): (deoxyuridine triphosphatase) This gene encodes an essential enzyme of nucleotide metabolism. The encoded protein forms a ubiquitous, homotetrameric enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This reaction serves two cellular purposes: providing a precursor (dUMP) for the synthesis of thymine nucleotides needed for DNA replication, and limiting intracellular pools of dUTP. Elevated levels of dUTP lead to increased incorporation of uracil into DNA, which induces extensive excision repair mediated by uracil glycosylase. This repair process, resulting in the removal and reincorporation of dUTP, is self-defeating and leads to DNA fragmentation and cell death. Alternative splicing of this gene leads to different isoforms that localize to either the mitochondrion or nucleus. A related pseudogene is located on chromosome 19. [provided by RefSeq, Jul 2008]

DUT links:

DUT-AS1 (HGNC:55420): (DUT antisense RNA 1)

DUT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 15-48331804-G-A is Benign according to our data. Variant chr15-48331804-G-A is described in ClinVar as Benign. ClinVar VariationId is 1336417.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025248.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DUT	NM_001025248.2	MANE Select	c.280+9G>A	intron	N/A	NP_001020419.1	P33316-3
DUT	NM_001330286.2		c.26-464G>A	intron	N/A	NP_001317215.1	H0YNW5
DUT	NM_001025249.1		c.-54+325G>A	intron	N/A	NP_001020420.1	P33316

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DUT	ENST00000331200.8	TSL:1 MANE Select	c.280+9G>A	intron	N/A	ENSP00000370376.2	P33316-3
DUT	ENST00000915906.1		c.280+9G>A	intron	N/A	ENSP00000585965.1
DUT	ENST00000949573.1		c.280+9G>A	intron	N/A	ENSP00000619632.1

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

596

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

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:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000104

AC:

AN:

9614

AF XY:

0.000195

show subpopulations

Gnomad AFR exome

AF:

0.00581

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:

0.000341

AC:

414

AN:

1213826

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

162

AN XY:

585402

show subpopulations

African (AFR)

AF:

0.0152

AC:

361

AN:

23792

American (AMR)

AF:

0.000261

AC:

AN:

11502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17022

East Asian (EAS)

AF:

0.00

AC:

AN:

27886

South Asian (SAS)

AF:

0.0000952

AC:

AN:

52498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29490

Middle Eastern (MID)

AF:

0.000281

AC:

AN:

3558

European-Non Finnish (NFE)

AF:

0.00000601

AC:

AN:

997800

Other (OTH)

AF:

0.000756

AC:

AN:

50278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00394

AC:

599

AN:

152010

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

295

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0141

AC:

583

AN:

41466

American (AMR)

AF:

0.000785

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67952

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00409

Hom.:

Bravo

AF:

0.00472

ClinVar

ClinVar submissions

Significance:Benign

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.45

(source)

DANN

Benign

0.82

PhyloP100

-3.6

PromoterAI

-0.085

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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