Genetic Variant UTP3:p.Asn28Asn (chr4-70688761-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020368.3(UTP3):c.84T>C(p.Asn28Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,438 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 22 hom. )

Consequence

UTP3
NM_020368.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.15

Publications

3 publications found

Variant links:

Genes affected

UTP3 (HGNC:24477): (UTP3 small subunit processome component) Enables RNA binding activity. Predicted to be involved in brain development and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

UTP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 4-70688761-T-C is Benign according to our data. Variant chr4-70688761-T-C is described in ClinVar as Benign. ClinVar VariationId is 790000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00891 (1351/151558) while in subpopulation AFR AF = 0.0301 (1242/41286). AF 95% confidence interval is 0.0287. There are 15 homozygotes in GnomAd4. There are 598 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020368.3. 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
	UTP3	NM_020368.3	MANE Select	c.84T>C	p.Asn28Asn	synonymous	Exon 1 of 1	NP_065101.1	Q9NQZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP3	ENST00000254803.4	TSL:6 MANE Select	c.84T>C	p.Asn28Asn	synonymous	Exon 1 of 1	ENSP00000254803.2	Q9NQZ2

Frequencies

GnomAD3 genomes

AF:

0.00891

AC:

1349

AN:

151440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00527

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00870

GnomAD2 exomes

AF:

0.00220

AC:

554

AN:

251432

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000967

AC:

1413

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000802

AC XY:

583

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0303

AC:

1015

AN:

33480

American (AMR)

AF:

0.00195

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000162

AC:

180

AN:

1112008

Other (OTH)

AF:

0.00179

AC:

108

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00891

AC:

1351

AN:

151558

Hom.:

Cov.:

AF XY:

0.00808

AC XY:

598

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.0301

AC:

1242

AN:

41286

American (AMR)

AF:

0.00526

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10480

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67898

Other (OTH)

AF:

0.00861

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

(source)

DANN

Benign

0.41

PhyloP100

-2.1

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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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