7-76515243-T-C

Variant summary

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

The NM_001347684.2(UPK3B):c.*39T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,575,898 control chromosomes in the GnomAD database, including 784,655 homozygotes. 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 0.99 (74367 hom., cov: 32)
  • Exomes 𝑓: 1.0 (710288 hom.)
• Consequence: UPK3B NM_001347684.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

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=1.7234967E-6).
• 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.*39T>C		3_prime_UTR_variant	6/6	ENST00000334348.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPK3B	ENST00000334348.8	c.*39T>C		3_prime_UTR_variant	6/6	2	NM_001347684.2	P1
UPK3B	ENST00000257632.9	c.955T>C	p.Trp319Arg	missense_variant	4/4	2
UPK3B	ENST00000394849.1	c.790T>C	p.Trp264Arg	missense_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150341 AN: 152094 Hom.: 74311 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.992

GnomAD3 exomes AF: 0.997 AC: 189214 AN: 189756 Hom.: 94339 AF XY: 0.998 AC XY: 101664 AN XY: 101890

Gnomad AFR exome AF: 0.959

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

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: 1422116 AN: 1423686 Hom.: 710288 Cov.: 80 AF XY: 0.999 AC XY: 703865 AN XY: 704522

Gnomad4 AFR exome AF: 0.961

Gnomad4 AMR exome AF: 0.997

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: 0.988 AC: 150456 AN: 152212 Hom.: 74367 Cov.: 32 AF XY: 0.989 AC XY: 73570 AN XY: 74422

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.995

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.992

Alfa AF: 0.998 Hom.: 119645

Bravo AF: 0.987

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.961 AC: 4213

ESP6500EA AF: 0.999 AC: 8561

ExAC AF: 0.995 AC: 116141

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.15
Dann	Benign	0.24
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0000017	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.35	N;N
REVEL	Benign	0.042
Sift	Benign	1.0	T;T
Sift4G	Benign	0.86	T;T
Polyphen		0.0	B;B
Vest4		0.014
MutPred		0.23		Gain of solvent accessibility (P = 6e-04);.;
ClinPred		0.00088	T
GERP RS		-5.8
Varity_R		0.033

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1799126; hg19: chr7-76144560; COSMIC: COSV57537004; COSMIC: COSV57537004;