dbSNP rs558490093: UPK3A:c.*107T>C (chr22-45295826-T-C) – 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.*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
NM_006953.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2B:1

Conservation

PhyloP100: -0.110

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:

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=-0.87).

BS2

High AC in GnomAd4 at 238 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.*107T>C		3_prime_UTR	Exon 6 of 6	NP_008884.1	O75631-1
	UPK3A	NM_001167574.2		c.*107T>C		3_prime_UTR	Exon 4 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.*107T>C	3_prime_UTR	Exon 6 of 6	ENSP00000216211.4	O75631-1
UPK3A	ENST00000957030.1		c.*107T>C	3_prime_UTR	Exon 6 of 6	ENSP00000627089.1
UPK3A	ENST00000938588.1		c.*107T>C	3_prime_UTR	Exon 3 of 3	ENSP00000608647.1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152198

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00253

AC XY:

1510

AN XY:

597986

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

26860

American (AMR)

AF:

0.000409

AC:

AN:

39128

Ashkenazi Jewish (ASJ)

AF:

0.000334

AC:

AN:

23970

East Asian (EAS)

AF:

0.00

AC:

AN:

36426

South Asian (SAS)

AF:

0.000936

AC:

AN:

77970

European-Finnish (FIN)

AF:

0.000705

AC:

AN:

41154

Middle Eastern (MID)

AF:

0.000253

AC:

AN:

3952

European-Non Finnish (NFE)

AF:

0.00309

AC:

2721

AN:

881714

Other (OTH)

AF:

0.00193

AC:

AN:

51244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

151

302

452

603

754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00156

AC:

238

AN:

152316

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41578

American (AMR)

AF:

0.000785

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00288

AC:

196

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.00180

Hom.:

Bravo

AF:

0.00173

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Renal hypodysplasia/aplasia 1 (2)

UPK3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.52

(source)

DANN

Benign

0.60

PhyloP100

-0.11

Mutation Taster

=100/0

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

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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