Genetic Variant UCN3:p.Gly88Val (chr10-5373983-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053049.4(UCN3):c.263G>T(p.Gly88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G88S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UCN3
NM_053049.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.321

Publications

0 publications found

Variant links:

Genes affected

UCN3 (HGNC:17781): (urocortin 3) This gene encodes a member of the sauvagine/corticotropin-releasing factor/urotensin I family of proteins. The encoded preproprotein is proteolytically processed to generate the mature peptide hormone, which is secreted by pancreatic beta and alpha cells. This hormone is an endogenous ligand for corticotropin-releasing factor receptor 2 and may regulate insulin secretion in response to plasma glucose levels. Patients with type 2 diabetes exhibit reduced levels of the encoded protein in beta cells. In the brain, the encoded protein may be responsible for the effects of stress on appetite. [provided by RefSeq, May 2016]

UCN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13762695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCN3	NM_053049.4 link	c.263G>T	p.Gly88Val	missense_variant	Exon 2 of 2	ENST00000380433.5	NP_444277.2	Q969E3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCN3	ENST00000380433.5 link	c.263G>T	p.Gly88Val	missense_variant	Exon 2 of 2	1	NM_053049.4	ENSP00000369798.3		Q969E3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725304

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

44190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

85686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110512

Other (OTH)

AF:

0.00

AC:

AN:

60210

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.45

M_CAP

Benign

0.0069

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.32

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.025

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

0.84

Vest4

0.18

MutPred

0.24

Gain of solvent accessibility (P = 0.1133);

MVP

0.068

MPC

0.31

ClinPred

0.76

GERP RS

0.41

Varity_R

0.098

gMVP

0.12

Mutation Taster

=91/9

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over