rs1799125

chr7-76515138-A-Cchr7-76515138-A-Gchr7-76515138-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

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 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	UniProt
UPK3B	NM_001347684.2	c.765A>C	p.Arg255Ser	missense_variant	6/6	ENST00000334348.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPK3B	ENST00000334348.8	c.765A>C	p.Arg255Ser	missense_variant	6/6	2	NM_001347684.2	P1
UPK3B	ENST00000257632.9	c.850A>C	p.Arg284=	synonymous_variant	4/4	2
UPK3B	ENST00000394849.1	c.685A>C	p.Arg229=	synonymous_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.989 AC: 150332 AN: 152062 Hom.: 74316 Cov.: 31

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

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.: 90 AF XY: 0.999 AC XY: 718221 AN XY: 718884

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.: 31 AF XY: 0.989 AC XY: 73557 AN XY: 74400

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	T
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	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	9.2e-7	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PROVEAN	Benign	1.5	N
REVEL	Benign	0.077
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.14
MutPred		0.30		Loss of solvent accessibility (P = 0.001);
ClinPred		0.0028	T
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

Other links and lift over

dbSNP: rs1799125; hg19: chr7-76144455;