chr7-76511879-A-G

Variant names:

• chr7-76511879-A-G
• rs1031096709
• NM_001347684.2:c.458A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001347684.2(UPK3B):​c.458A>G​(p.Tyr153Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,392,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: UPK3B NM_001347684.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 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]

ENSG00000297839 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050201237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347684.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3B	NM_001347684.2	MANE Select	c.458A>G	p.Tyr153Cys	missense	Exon 3 of 6	NP_001334613.1	Q9BT76-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3B	ENST00000334348.8	TSL:2 MANE Select	c.458A>G	p.Tyr153Cys	missense	Exon 3 of 6	ENSP00000334938.3	Q9BT76-3
	UPK3B	ENST00000257632.9	TSL:2	c.623A>G	p.Tyr208Cys	missense	Exon 2 of 4	ENSP00000257632.5	Q9BT76-1
	UPK3B	ENST00000911147.1		c.458A>G	p.Tyr153Cys	missense	Exon 3 of 6	ENSP00000581206.1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 75 AN: 150424 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000487

GnomAD2 exomes AF: 0.000295 AC: 14 AN: 47524 AF XY: 0.000292

Gnomad AFR exome AF: 0.00335

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000636 AC: 79 AN: 1241714 Hom.: 0 Cov.: 22 AF XY: 0.0000432 AC XY: 26 AN XY: 602336

African (AFR) AF: 0.00260 AC: 70 AN: 26956

American (AMR) AF: 0.000102 AC: 2 AN: 19642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18460

East Asian (EAS) AF: 0.00 AC: 0 AN: 34076

South Asian (SAS) AF: 0.00 AC: 0 AN: 62082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3502

European-Non Finnish (NFE) AF: 0.00000202 AC: 2 AN: 989892

Other (OTH) AF: 0.0000967 AC: 5 AN: 51698

GnomAD4 genome AF: 0.000492 AC: 74 AN: 150546 Hom.: 0 Cov.: 28 AF XY: 0.000436 AC XY: 32 AN XY: 73458

African (AFR) AF: 0.00175 AC: 72 AN: 41178

American (AMR) AF: 0.0000661 AC: 1 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4976

South Asian (SAS) AF: 0.00 AC: 0 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67400

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000674 Hom.: 0

Bravo AF: 0.000654

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.0033
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.050	T
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.023	B
Vest4		0.72
MVP		0.55
ClinPred		0.13	T
GERP RS		5.2
Varity_R		0.21
gMVP		0.87
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1031096709; hg19: chr7-76141196;