Genetic Variant NM_198152.5:c.122A>C (chr3-191278152-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198152.5(UTS2B):c.122A>C(p.Asp41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UTS2B
NM_198152.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05402264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5 link	c.122A>C	p.Asp41Ala	missense_variant	Exon 6 of 9	ENST00000340524.10	NP_937795.2	Q765I0
UTS2B	XM_017006091.2 link	c.122A>C	p.Asp41Ala	missense_variant	Exon 5 of 8		XP_016861580.1	F8WCV4
UTS2B	XM_011512631.3 link	c.122A>C	p.Asp41Ala	missense_variant	Exon 5 of 8		XP_011510933.1	Q765I0
UTS2B	XM_047447899.1 link	c.122A>C	p.Asp41Ala	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.122A>C	p.Asp41Ala	missense_variant	Exon 6 of 9	2	NM_198152.5	ENSP00000340526.5		Q765I0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000524

AC:

AN:

190850

AF XY:

0.00000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000706

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1388810

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30106

American (AMR)

AF:

0.00

AC:

AN:

30770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24020

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37756

South Asian (SAS)

AF:

0.00

AC:

AN:

75982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075500

Other (OTH)

AF:

0.0000175

AC:

AN:

57148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 17, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.122A>C (p.D41A) alteration is located in exon 6 (coding exon 2) of the UTS2B gene. This alteration results from a A to C substitution at nucleotide position 122, causing the aspartic acid (D) at amino acid position 41 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.0

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.33

.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PhyloP100

0.34

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.034

Sift

Benign

0.39

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.053

B;B

Vest4

0.15

MutPred

0.25

Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);

MVP

0.030

MPC

0.070

ClinPred

0.023

GERP RS

1.9

Varity_R

0.060

gMVP

0.11

Mutation Taster

=81/19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_198152.5:c.122A>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over