rs558490093

Positions:

• chr22-45295826-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000216211.9(UPK3A):​c.*107T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,334,734 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: UPK3A ENST00000216211.9 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2 B:1
• Conservation: PhyloP100: -0.110

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.*107T>C		3_prime_UTR_variant	6/6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.*107T>C		3_prime_UTR_variant	4/4		NP_001161046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9	c.*107T>C		3_prime_UTR_variant	6/6	1	NM_006953.4	ENSP00000216211	P1
UPK3A	ENST00000396082.2			downstream_gene_variant		1		ENSP00000379391

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152198 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00250 AC: 2958 AN: 1182418 Hom.: 9 Cov.: 16 AF XY: 0.00253 AC XY: 1510 AN XY: 597986

Gnomad4 AFR exome AF: 0.000410

Gnomad4 AMR exome AF: 0.000409

Gnomad4 ASJ exome AF: 0.000334

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000936

Gnomad4 FIN exome AF: 0.000705

Gnomad4 NFE exome AF: 0.00309

Gnomad4 OTH exome AF: 0.00193

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152316 Hom.: 1 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74490

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00288

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00173

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal hypodysplasia/aplasia 1 Uncertain:2

Uncertain significance, no assertion criteria provided	literature only	OMIM	Jul 01, 2005	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

UPK3A-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 19, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.52
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs558490093; hg19: chr22-45691707;