chr7-76511809-C-T

Variant names:

• chr7-76511809-C-T
• rs1188310365
• NM_001347684.2:c.388C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001347684.2(UPK3B):​c.388C>T​(p.Arg130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,546,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: UPK3B NM_001347684.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.482
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.388C>T	p.Arg130Trp	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.388C>T	p.Arg130Trp	missense	Exon 3 of 6	ENSP00000334938.3	Q9BT76-3
	UPK3B	ENST00000257632.9	TSL:2	c.553C>T	p.Arg185Trp	missense	Exon 2 of 4	ENSP00000257632.5	Q9BT76-1
	UPK3B	ENST00000911147.1		c.388C>T	p.Arg130Trp	missense	Exon 3 of 6	ENSP00000581206.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152046 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000276 AC: 4 AN: 145164 AF XY: 0.0000254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000866

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000115 AC: 16 AN: 1394502 Hom.: 0 Cov.: 32 AF XY: 0.00000582 AC XY: 4 AN XY: 687650

African (AFR) AF: 0.0000317 AC: 1 AN: 31518

American (AMR) AF: 0.00 AC: 0 AN: 35402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24704

East Asian (EAS) AF: 0.00 AC: 0 AN: 36308

South Asian (SAS) AF: 0.0000503 AC: 4 AN: 79542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00000836 AC: 9 AN: 1076940

Other (OTH) AF: 0.0000348 AC: 2 AN: 57536

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152046 Hom.: 0 Cov.: 28 AF XY: 0.0000269 AC XY: 2 AN XY: 74270

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000151

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	Benign	0.29
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.078
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.48
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.68		Loss of disorder (P = 0.0096)
MVP		0.67
ClinPred		0.54	D
GERP RS		4.3
Varity_R		0.61
gMVP		0.67
Mutation Taster		=82/18	polymorphism

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: rs1188310365; hg19: chr7-76141126; COSMIC: COSV57536699;