rs2673087

Variant names:

• chr22-45287094-A-G
• rs2673087
• NM_006953.4:c.209-78A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-45287094-A-G
• chr22-45287094-A-C
• chr22-45287094-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3A	NM_006953.4	MANE Select	c.209-78A>G		intron	N/A	NP_008884.1	O75631-1
	UPK3A	NM_001167574.2		c.208+998A>G		intron	N/A	NP_001161046.1	O75631-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3A	ENST00000216211.9	TSL:1 MANE Select	c.209-78A>G		intron	N/A	ENSP00000216211.4	O75631-1
	UPK3A	ENST00000396082.2	TSL:1	c.208+998A>G		intron	N/A	ENSP00000379391.2	O75631-2
	UPK3A	ENST00000957030.1		c.209-78A>G		intron	N/A	ENSP00000627089.1

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

African (AFR) AF: 0.819 AC: 27174 AN: 33198

American (AMR) AF: 0.842 AC: 37629 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 21664 AN: 26072

East Asian (EAS) AF: 0.767 AC: 30403 AN: 39642

South Asian (SAS) AF: 0.762 AC: 65240 AN: 85588

European-Finnish (FIN) AF: 0.741 AC: 36152 AN: 48820

Middle Eastern (MID) AF: 0.752 AC: 3342 AN: 4442

European-Non Finnish (NFE) AF: 0.767 AC: 847546 AN: 1104830

Other (OTH) AF: 0.774 AC: 46394 AN: 59912

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

African (AFR) AF: 0.815 AC: 33838 AN: 41508

American (AMR) AF: 0.807 AC: 12333 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3804 AN: 5164

South Asian (SAS) AF: 0.749 AC: 3617 AN: 4826

European-Finnish (FIN) AF: 0.739 AC: 7809 AN: 10574

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52282 AN: 67978

Other (OTH) AF: 0.774 AC: 1632 AN: 2108

Alfa AF: 0.775 Hom.: 174282

Bravo AF: 0.793

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.32
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2673087; hg19: chr22-45682975;