Genetic Variant UPK3A:c.-26C>G (chr22-45284988-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006953.4(UPK3A):c.-26C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,528,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

UPK3A
NM_006953.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

Publications

0 publications found

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 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

UPK3A links:

ENSG00000301739 (HGNC:):

ENSG00000301739 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BS2

High AC in GnomAd4 at 29 AD gene.

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.-26C>G		5_prime_UTR	Exon 1 of 6	NP_008884.1	O75631-1
	UPK3A	NM_001167574.2		c.-26C>G		5_prime_UTR	Exon 1 of 4	NP_001161046.1	O75631-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UPK3A	ENST00000216211.9	TSL:1 MANE Select	c.-26C>G	5_prime_UTR	Exon 1 of 6	ENSP00000216211.4	O75631-1
UPK3A	ENST00000957030.1		c.-26C>G	5_prime_UTR	Exon 1 of 6	ENSP00000627089.1
UPK3A	ENST00000938588.1		c.-26C>G	5_prime_UTR	Exon 1 of 3	ENSP00000608647.1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000239

AC:

AN:

125532

AF XY:

0.000174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000412

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000648

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

192

AN:

1376734

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

679180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30904

American (AMR)

AF:

0.0000845

AC:

AN:

35498

Ashkenazi Jewish (ASJ)

AF:

0.00248

AC:

AN:

24954

East Asian (EAS)

AF:

0.00

AC:

AN:

35412

South Asian (SAS)

AF:

0.0000635

AC:

AN:

78794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33428

Middle Eastern (MID)

AF:

0.000246

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.0000938

AC:

101

AN:

1076212

Other (OTH)

AF:

0.000348

AC:

AN:

57466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000191

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41450

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000249

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Renal hypodysplasia/aplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.9

(source)

DANN

Benign

0.89

PhyloP100

-0.041

PromoterAI

0.061

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over