7-76511744-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPK3B	NM_001347684.2	c.323C>T	p.Pro108Leu	missense_variant	3/6	ENST00000334348.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPK3B	ENST00000334348.8	c.323C>T	p.Pro108Leu	missense_variant	3/6	2	NM_001347684.2	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245500 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133336

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 SAS 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: 13 AN: 1459050 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 725662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.488C>T (p.P163L) alteration is located in exon 2 (coding exon 2) of the UPK3B gene. This alteration results from a C to T substitution at nucleotide position 488, causing the proline (P) at amino acid position 163 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	0.94	D;D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.084	T;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		1.0, 0.99	.;D;D
Vest4		0.55
MutPred		0.38		.;Loss of disorder (P = 0.0163);.;
MVP		0.35
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1302184499; hg19: chr7-76141061;