Genetic Variant NM_018949.3:c.361G>T (chr17-82374685-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018949.3(UTS2R):c.361G>T(p.Val121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,358 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

UTS2R
NM_018949.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0880

Variant links:

Genes affected

UTS2R (HGNC:4468): (urotensin 2 receptor) Predicted to enable urotensin II receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UTS2R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033631027).

BP6

Variant 17-82374685-G-T is Benign according to our data. Variant chr17-82374685-G-T is described in ClinVar as [Benign]. Clinvar id is 781393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2066/152342) while in subpopulation AFR AF= 0.0461 (1915/41570). AF 95% confidence interval is 0.0443. There are 59 homozygotes in gnomad4. There are 1020 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2R	NM_018949.3 link	c.361G>T	p.Val121Leu	missense_variant	Exon 3 of 3	ENST00000313135.5	NP_061822.1	Q9UKP6
UTS2R	NM_001381897.1 link	c.361G>T	p.Val121Leu	missense_variant	Exon 2 of 2		NP_001368826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2R	ENST00000313135.5 link	c.361G>T	p.Val121Leu	missense_variant	Exon 3 of 3	6	NM_018949.3	ENSP00000323516.2		Q9UKP6

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2064

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0461

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00349

AC:

869

AN:

249286

Hom.:

AF XY:

0.00278

AC XY:

376

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.0466

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00140

AC:

2046

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

862

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.0136

AC:

2066

AN:

152342

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1020

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.0151

ESP6500AA

AF:

0.0422

AC:

186

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00409

AC:

496

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 04, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.78

REVEL

Benign

0.14

Sift

Benign

0.35

Sift4G

Benign

0.49

Polyphen

0.12

Vest4

0.037

MutPred

0.60

Gain of helix (P = 0.132);

MVP

0.65

MPC

0.41

ClinPred

0.0021

GERP RS

3.0

Varity_R

0.21

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over