Variant 22-45284989-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006953.4(UPK3A):c.-25G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,528,842 control chromosomes in the GnomAD database, including 1,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 838 hom., cov: 33)

Exomes 𝑓: 0.021 ( 1128 hom. )

Consequence

UPK3A
NM_006953.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.321

Variant links:

Genes affected

UPK3A (HGNC:12580): (uroplakin 3A) This gene encodes a member of the uroplakin family, a group of transmembrane proteins that form complexes on the apical surface of the bladder epithelium. Mutations in this gene may be associated with renal adysplasia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

UPK3A 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 (BayesDel_noAF=-0.67).

BP6

Variant 22-45284989-G-C is Benign according to our data. Variant chr22-45284989-G-C is described in ClinVar as [Benign]. Clinvar id is 341968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4 link	c.-25G>C		5_prime_UTR_variant	1/6	ENST00000216211.9	NP_008884.1	O75631-1
UPK3A	NM_001167574.2 link	c.-25G>C		5_prime_UTR_variant	1/4		NP_001161046.1	O75631-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211 link	c.-25G>C		5_prime_UTR_variant	1/6	1	NM_006953.4	ENSP00000216211.4		O75631-1
UPK3A	ENST00000396082.2 link	c.-25G>C		upstream_gene_variant		1		ENSP00000379391.2		O75631-2

Frequencies

GnomAD3 genomes

AF:

0.0681

AC:

10356

AN:

152160

Hom.:

837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.0525

GnomAD3 exomes

AF:

0.0340

AC:

4269

AN:

125414

Hom.:

227

AF XY:

0.0330

AC XY:

2269

AN XY:

68756

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.00544

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0214

AC:

29508

AN:

1376574

Hom.:

1128

Cov.:

AF XY:

0.0212

AC XY:

14412

AN XY:

679096

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.00616

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0681

AC:

10366

AN:

152268

Hom.:

838

Cov.:

AF XY:

0.0670

AC XY:

4990

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.0437

Gnomad4 FIN

AF:

0.00640

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0770

Asia WGS

AF:

0.0800

AC:

277

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal hypodysplasia/aplasia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.5

DANN

Benign

0.87

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