chr7-76515138-A-C

Variant names:

• chr7-76515138-A-C
• rs1799125
• NM_001347684.2:c.765A>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.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. 14/18 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
• Publications: 17 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=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 rank	MANE	Protein	UniProt
UPK3B	NM_001347684.2	c.765A>C	p.Arg255Ser	missense_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.765A>C	p.Arg255Ser	missense_variant	Exon 6 of 6	2	NM_001347684.2	ENSP00000334938.3
UPK3B	ENST00000257632.9	c.850A>C	p.Arg284Arg	synonymous_variant	Exon 4 of 4	2		ENSP00000257632.5
UPK3B	ENST00000394849.1	c.685A>C	p.Arg229Arg	synonymous_variant	Exon 5 of 5	2		ENSP00000378319.1

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

GnomAD2 exomes AF: 0.997 AC: 223106 AN: 223750 AF XY: 0.998

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 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

African (AFR) AF: 0.962 AC: 32067 AN: 33324

American (AMR) AF: 0.998 AC: 42490 AN: 42590

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25696 AN: 25696

East Asian (EAS) AF: 1.00 AC: 39008 AN: 39018

South Asian (SAS) AF: 1.00 AC: 83931 AN: 83942

European-Finnish (FIN) AF: 1.00 AC: 51069 AN: 51070

Middle Eastern (MID) AF: 0.998 AC: 5737 AN: 5750

European-Non Finnish (NFE) AF: 1.00 AC: 1106373 AN: 1106414

Other (OTH) AF: 0.998 AC: 59637 AN: 59784

GnomAD4 genome AF: 0.989 AC: 150447 AN: 152180 Hom.: 74372 Cov.: 31 AF XY: 0.989 AC XY: 73557 AN XY: 74400

African (AFR) AF: 0.961 AC: 39895 AN: 41522

American (AMR) AF: 0.995 AC: 15222 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5135 AN: 5142

South Asian (SAS) AF: 0.999 AC: 4821 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

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

European-Non Finnish (NFE) AF: 1.00 AC: 67994 AN: 68002

Other (OTH) AF: 0.993 AC: 2093 AN: 2108

Alfa AF: 0.998 Hom.: 42711

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
AlphaMissense	Benign	0.061
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
PhyloP100		-3.5
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

Other links and lift over

dbSNP: rs1799125; hg19: chr7-76144455; COSMIC: COSV99991107; COSMIC: COSV99991107;