Variant chr7-76515138-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001347684.2(UPK3B):c.765A>C(p.Arg255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,599,768 control chromosomes in the GnomAD database, including 796,600 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.99 ( 74372 hom., cov: 31)

Exomes 𝑓: 1.0 ( 722228 hom. )

Consequence

UPK3B
NM_001347684.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.52

Variant links:

Genes affected

UPK3B (HGNC:21444): (uroplakin 3B) UPK3B is a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b (UPK1B; MIM 602380), one of the major conserved urothelium membrane proteins. The other major conserved integral membrane proteins of urothelial plaques are UPK1A (MIM 611557), UPK2 (MIM 611558), and UPK3A (MIM 611559) (Deng et al., 2002 [PubMed 12446744]).[supplied by OMIM, Mar 2008]

UPK3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.1536225E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3B	NM_001347684.2 linkuse as main transcript	c.765A>C	p.Arg255Ser	missense_variant	6/6	ENST00000334348.8	NP_001334613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UPK3B	ENST00000334348.8 linkuse as main transcript	c.765A>C	p.Arg255Ser	missense_variant	6/6	2	NM_001347684.2	ENSP00000334938.3	Q9BT76-3
UPK3B	ENST00000257632.9 linkuse as main transcript	c.850A>C	p.Arg284Arg	synonymous_variant	4/4	2		ENSP00000257632.5	Q9BT76-1
UPK3B	ENST00000394849.1 linkuse as main transcript	c.685A>C	p.Arg229Arg	synonymous_variant	5/5	2		ENSP00000378319.1	Q9BT76-2

Frequencies

GnomAD3 genomes

AF:

0.989

AC:

150332

AN:

152062

Hom.:

74316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.993

GnomAD3 exomes

AF:

0.997

AC:

223106

AN:

223750

Hom.:

111236

AF XY:

0.998

AC XY:

121259

AN XY:

121530

show subpopulations

Gnomad AFR exome

AF:

0.960

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1446008

AN:

1447588

Hom.:

722228

Cov.:

AF XY:

0.999

AC XY:

718221

AN XY:

718884

show subpopulations

Gnomad4 AFR exome

AF:

0.962

Gnomad4 AMR exome

AF:

0.998

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.989

AC:

150447

AN:

152180

Hom.:

74372

Cov.:

AF XY:

0.989

AC XY:

73557

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.961

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.993

Alfa

AF:

0.999

Hom.:

37222

Bravo

AF:

0.987

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.961

AC:

4220

ESP6500EA

AF:

1.00

AC:

8578

ExAC

AF:

0.995

AC:

118601

Asia WGS

AF:

0.998

AC:

3468

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.0010

DANN

Benign

0.19

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.15

MetaRNN

Benign

9.2e-7

MetaSVM

Benign

-0.96

PROVEAN

Benign

1.5

REVEL

Benign

0.077

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.14

MutPred

0.30

Loss of solvent accessibility (P = 0.001);

ClinPred

0.0028

GERP RS

-7.0

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over