Genetic Variant UPK3B:c.86-15C>T (chr7-76510888-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001347684.2(UPK3B):c.86-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 1,594,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

UPK3B
NM_001347684.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.542

Publications

0 publications found

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:

ENSG00000297839 (HGNC:):

ENSG00000297839 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059850752).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347684.2. 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
	UPK3B	NM_001347684.2	MANE Select	c.86-15C>T		intron	N/A	NP_001334613.1	Q9BT76-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UPK3B	ENST00000334348.8	TSL:2 MANE Select	c.86-15C>T		intron	N/A	ENSP00000334938.3	Q9BT76-3
UPK3B	ENST00000257632.9	TSL:2	c.236C>T	p.Ser79Phe	missense	Exon 1 of 4	ENSP00000257632.5	Q9BT76-1
UPK3B	ENST00000911147.1		c.86-15C>T		intron	N/A	ENSP00000581206.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1441874

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715938

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

32988

American (AMR)

AF:

0.00

AC:

AN:

41518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25734

East Asian (EAS)

AF:

0.00

AC:

AN:

38168

South Asian (SAS)

AF:

0.00

AC:

AN:

83774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5186

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1103460

Other (OTH)

AF:

0.00

AC:

AN:

59598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.00000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.3

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.34

M_CAP

Benign

0.0097

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.54

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

REVEL

Benign

0.031

Sift

Benign

0.041

Sift4G

Uncertain

0.048

Polyphen

0.66

Vest4

0.048

MutPred

0.36

Gain of catalytic residue at S79 (P = 0.0095)

MVP

0.030

ClinPred

0.12

GERP RS

1.4

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.045

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over