Genetic Variant UTS2B:p.Arg47His (chr3-191278134-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198152.5(UTS2B):c.140G>A(p.Arg47His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,559,766 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

UTS2B
NM_198152.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.99

Publications

2 publications found

Variant links:

Genes affected

UTS2B (HGNC:30894): (urotensin 2B) Predicted to enable G protein-coupled receptor binding activity. Predicted to be involved in regulation of blood pressure. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

UTS2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02344051).

BP6

Variant 3-191278134-C-T is Benign according to our data. Variant chr3-191278134-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2463051.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5 link	c.140G>A	p.Arg47His	missense_variant	Exon 6 of 9	ENST00000340524.10	NP_937795.2	Q765I0
UTS2B	XM_017006091.2 link	c.140G>A	p.Arg47His	missense_variant	Exon 5 of 8		XP_016861580.1	F8WCV4
UTS2B	XM_011512631.3 link	c.140G>A	p.Arg47His	missense_variant	Exon 5 of 8		XP_011510933.1	Q765I0
UTS2B	XM_047447899.1 link	c.140G>A	p.Arg47His	missense_variant	Exon 5 of 8		XP_047303855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10 link	c.140G>A	p.Arg47His	missense_variant	Exon 6 of 9	2	NM_198152.5	ENSP00000340526.5		Q765I0

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.000133

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000529

AC:

AN:

207910

AF XY:

0.0000616

show subpopulations

Gnomad AFR exome

AF:

0.0000738

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000610

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1407948

Hom.:

Cov.:

AF XY:

0.0000486

AC XY:

AN XY:

700188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30680

American (AMR)

AF:

0.00

AC:

AN:

34496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24764

East Asian (EAS)

AF:

0.00

AC:

AN:

37010

South Asian (SAS)

AF:

0.0000520

AC:

AN:

76858

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52128

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.0000496

AC:

AN:

1088532

Other (OTH)

AF:

0.0000691

AC:

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151818

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41366

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67840

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0030

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0069

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.23

.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PhyloP100

-2.0

PrimateAI

Benign

0.18

PROVEAN

Benign

1.8

N;N

REVEL

Benign

0.019

Sift

Benign

0.66

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;B

Vest4

0.099

MutPred

0.22

Gain of glycosylation at T45 (P = 0.0591);Gain of glycosylation at T45 (P = 0.0591);

MVP

0.055

MPC

0.069

ClinPred

0.016

GERP RS

-8.6

Varity_R

0.015

gMVP

0.060

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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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chr3-191278134-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over