Variant 1-7847858-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006786.4(UTS2):c.283C>A(p.Pro95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,612,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

UTS2
NM_006786.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

UTS2 (HGNC:12636): (urotensin 2) This gene encodes a mature peptide that is an active cyclic heptapeptide absolutely conserved from lamprey to human. The active peptide acts as a vasoconstrictor and is expressed only in brain tissue. Despite the gene family name similarity, this gene is not homologous to urocortin, a member of the sauvagine/corticotropin-releasing factor/urotensin I family. Most of the proprotein is cleaved to make the mature peptide. Transcript variants encoding different preproprotein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

UTS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091742694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTS2	NM_006786.4 linkuse as main transcript	c.283C>A	p.Pro95Thr	missense_variant	4/4	ENST00000361696.10	NP_006777.1	O95399-1
UTS2	NM_021995.2 linkuse as main transcript	c.328C>A	p.Pro110Thr	missense_variant	5/5		NP_068835.1	O95399-2A0AVP6
UTS2	XM_011540537.3 linkuse as main transcript	c.328C>A	p.Pro110Thr	missense_variant	6/6		XP_011538839.1	O95399-2
UTS2	XM_011540538.2 linkuse as main transcript	c.283C>A	p.Pro95Thr	missense_variant	5/5		XP_011538840.1	O95399-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UTS2	ENST00000361696.10 linkuse as main transcript	c.283C>A	p.Pro95Thr	missense_variant	4/4	1	NM_006786.4	ENSP00000355163.5	O95399-1
UTS2	ENST00000054668.5 linkuse as main transcript	c.328C>A	p.Pro110Thr	missense_variant	5/5	1		ENSP00000054668.5	O95399-2
UTS2	ENST00000377516.6 linkuse as main transcript	c.283C>A	p.Pro95Thr	missense_variant	5/7	5		ENSP00000366738.2	Q5H8X8

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

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:

0.000588

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000372

AC:

AN:

250240

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000671

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000697

AC:

1018

AN:

1460650

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

487

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000471

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000867

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000375

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000502

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.328C>A (p.P110T) alteration is located in exon 5 (coding exon 5) of the UTS2 gene. This alteration results from a C to A substitution at nucleotide position 328, causing the proline (P) at amino acid position 110 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.29

.;T;.

Eigen

Benign

0.065

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

.;L;.

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.095

Sift

Benign

0.049

D;D;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.99

D;P;D

Vest4

0.37

MVP

0.52

MPC

0.42

ClinPred

0.18

GERP RS

3.7

Varity_R

0.13

gMVP

0.042

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

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