Genetic Variant NM_001347684.2:c.323C>T (chr7-76511744-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001347684.2(UPK3B):c.323C>T(p.Pro108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

UPK3B
NM_001347684.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

1 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.323C>T	p.Pro108Leu	missense	Exon 3 of 6	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.323C>T	p.Pro108Leu	missense	Exon 3 of 6	ENSP00000334938.3	Q9BT76-3
UPK3B	ENST00000257632.9	TSL:2	c.488C>T	p.Pro163Leu	missense	Exon 2 of 4	ENSP00000257632.5	Q9BT76-1
UPK3B	ENST00000911147.1		c.323C>T	p.Pro108Leu	missense	Exon 3 of 6	ENSP00000581206.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245500

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459050

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725662

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

85934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4908

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111278

Other (OTH)

AF:

0.0000166

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.18

Sift

Benign

0.084

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.55

MutPred

0.38

Loss of disorder (P = 0.0163)

MVP

0.35

ClinPred

0.79

GERP RS

4.3

Varity_R

0.12

gMVP

0.44

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over