chr22-45290209-G-A

Variant names:

• chr22-45290209-G-A
• rs3788643
• NM_006953.4:c.571+1066G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006953.4(UPK3A):​c.571+1066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,090 control chromosomes in the GnomAD database, including 2,103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2103 hom., cov: 32)
• Consequence: UPK3A NM_006953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3A	NM_006953.4	MANE Select	c.571+1066G>A		intron	N/A	NP_008884.1
	UPK3A	NM_001167574.2		c.209-2972G>A		intron	N/A	NP_001161046.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3A	ENST00000216211.9	TSL:1 MANE Select	c.571+1066G>A		intron	N/A	ENSP00000216211.4
	UPK3A	ENST00000396082.2	TSL:1	c.209-2972G>A		intron	N/A	ENSP00000379391.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24975 AN: 151972 Hom.: 2098 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24998 AN: 152090 Hom.: 2103 Cov.: 32 AF XY: 0.163 AC XY: 12098 AN XY: 74362

African (AFR) AF: 0.191 AC: 7930 AN: 41484

American (AMR) AF: 0.158 AC: 2419 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3466

East Asian (EAS) AF: 0.234 AC: 1207 AN: 5164

South Asian (SAS) AF: 0.157 AC: 755 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10247 AN: 67972

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.157 Hom.: 7507

Bravo AF: 0.168

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.34
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3788643; hg19: chr22-45686090;