chr22-45287094-A-G

Position:

• chr22-45287094-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006953.4(UPK3A):​c.209-78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,599,322 control chromosomes in the GnomAD database, including 477,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46689 hom., cov: 32)
  • Exomes 𝑓: 0.77 (430702 hom.)
• Consequence: UPK3A NM_006953.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.69

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-45287094-A-G is Benign according to our data. Variant chr22-45287094-A-G is described in ClinVar as [Benign]. Clinvar id is 1237634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.209-78A>G		intron_variant		ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.208+998A>G		intron_variant			NP_001161046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9	c.209-78A>G		intron_variant		1	NM_006953.4	ENSP00000216211.4
UPK3A	ENST00000396082.2	c.208+998A>G		intron_variant		1		ENSP00000379391.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119080 AN: 151994 Hom.: 46651 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.776

GnomAD4 exome AF: 0.771 AC: 1115544 AN: 1447210 Hom.: 430702 AF XY: 0.771 AC XY: 555287 AN XY: 720614

Gnomad4 AFR exome AF: 0.819

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.831

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.762

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.774

GnomAD4 genome AF: 0.783 AC: 119176 AN: 152112 Hom.: 46689 Cov.: 32 AF XY: 0.782 AC XY: 58159 AN XY: 74362

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.774

Alfa AF: 0.774 Hom.: 73082

Bravo AF: 0.793

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2673087; hg19: chr22-45682975;