chr7-76515243-T-C

Variant names:

• chr7-76515243-T-C
• rs1799126
• NM_001347684.2:c.*39T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UPK3B	NM_001347684.2	c.*39T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000334348.8	NP_001334613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK3B	ENST00000334348.8	c.*39T>C		3_prime_UTR_variant	Exon 6 of 6	2	NM_001347684.2	ENSP00000334938.3
UPK3B	ENST00000257632.9	c.955T>C	p.Trp319Arg	missense_variant	Exon 4 of 4	2		ENSP00000257632.5
UPK3B	ENST00000394849.1	c.790T>C	p.Trp264Arg	missense_variant	Exon 5 of 5	2		ENSP00000378319.1

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

GnomAD2 exomes AF: 0.997 AC: 189214 AN: 189756 AF XY: 0.998

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 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

African (AFR) AF: 0.961 AC: 31494 AN: 32758

American (AMR) AF: 0.997 AC: 39257 AN: 39356

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25392 AN: 25392

East Asian (EAS) AF: 1.00 AC: 37703 AN: 37704

South Asian (SAS) AF: 1.00 AC: 81210 AN: 81220

European-Finnish (FIN) AF: 1.00 AC: 49998 AN: 49998

Middle Eastern (MID) AF: 0.998 AC: 5643 AN: 5656

European-Non Finnish (NFE) AF: 1.00 AC: 1092668 AN: 1092704

Other (OTH) AF: 0.998 AC: 58751 AN: 58898

GnomAD4 genome AF: 0.988 AC: 150456 AN: 152212 Hom.: 74367 Cov.: 32 AF XY: 0.989 AC XY: 73570 AN XY: 74422

African (AFR) AF: 0.960 AC: 39868 AN: 41522

American (AMR) AF: 0.995 AC: 15229 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3468 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.999 AC: 4817 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68005 AN: 68012

Other (OTH) AF: 0.992 AC: 2083 AN: 2100

Alfa AF: 0.998 Hom.: 144695

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;.
PhyloP100		-3.4
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

Other links and lift over

dbSNP: rs1799126; hg19: chr7-76144560; COSMIC: COSV57537004; COSMIC: COSV57537004;