dbSNP rs146162534: UCN3:p.Thr111Thr (chr10-5374053-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_053049.4(UCN3):c.333G>A(p.Thr111Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,078 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 13 hom., cov: 28)

Exomes 𝑓: 0.00070 ( 6 hom. )

Consequence

UCN3
NM_053049.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.401

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-5374053-G-A is Benign according to our data. Variant chr10-5374053-G-A is described in ClinVar as Benign. ClinVar VariationId is 784083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.401 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00669 (1016/151920) while in subpopulation AFR AF = 0.0234 (970/41418). AF 95% confidence interval is 0.0222. There are 13 homozygotes in GnomAd4. There are 474 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053049.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCN3	NM_053049.4	MANE Select	c.333G>A	p.Thr111Thr	synonymous	Exon 2 of 2	NP_444277.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCN3	ENST00000380433.5	TSL:1 MANE Select	c.333G>A	p.Thr111Thr	synonymous	Exon 2 of 2	ENSP00000369798.3	Q969E3

Frequencies

GnomAD3 genomes

AF:

0.00664

AC:

1008

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00170

AC:

422

AN:

248534

AF XY:

0.00118

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000698

AC:

1020

AN:

1461158

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

429

AN XY:

726812

show subpopulations

African (AFR)

AF:

0.0245

AC:

820

AN:

33462

American (AMR)

AF:

0.00146

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111680

Other (OTH)

AF:

0.00161

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00669

AC:

1016

AN:

151920

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

474

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0234

AC:

970

AN:

41418

American (AMR)

AF:

0.00242

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67914

Other (OTH)

AF:

0.00190

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00737

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.70

PhyloP100

-0.40

Mutation Taster

=100/0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over