rs145186308

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006953.4(UPK3A):c.202G>A(p.Asp68Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000861 in 1,614,110 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 2 hom. )

Consequence

UPK3A
NM_006953.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 2.15

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017673671).

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4 linkuse as main transcript	c.202G>A	p.Asp68Asn	missense_variant	2/6	ENST00000216211.9	NP_008884.1	O75631-1
UPK3A	NM_001167574.2 linkuse as main transcript	c.202G>A	p.Asp68Asn	missense_variant	2/4		NP_001161046.1	O75631-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9 linkuse as main transcript	c.202G>A	p.Asp68Asn	missense_variant	2/6	1	NM_006953.4	ENSP00000216211.4		O75631-1
UPK3A	ENST00000396082.2 linkuse as main transcript	c.202G>A	p.Asp68Asn	missense_variant	2/4	1		ENSP00000379391.2		O75631-2

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000513

AC:

129

AN:

251288

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000880

AC:

1286

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

605

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152292

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000663

Hom.:

Bravo

AF:

0.000669

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal hypodysplasia/aplasia 1

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Uncertain significance, criteria provided, single submitter	research	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	-	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

UPK3A: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.079

T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.097

Sift

Benign

0.24

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.017

B;B

Vest4

0.21

MVP

0.31

MPC

0.20

ClinPred

0.0055

GERP RS

2.8

Varity_R

0.043

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over