rs1188310365

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-76511809-C-G
• chr7-76511809-C-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>G​(p.Arg130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R130W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UPK3B NM_001347684.2 missense
• Clinical Significance: Not reported in ClinVar
• 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>G	p.Arg130Gly	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>G	p.Arg130Gly	missense	Exon 3 of 6	ENSP00000334938.3	Q9BT76-3
	UPK3B	ENST00000257632.9	TSL:2	c.553C>G	p.Arg185Gly	missense	Exon 2 of 4	ENSP00000257632.5	Q9BT76-1
	UPK3B	ENST00000911147.1		c.388C>G	p.Arg130Gly	missense	Exon 3 of 6	ENSP00000581206.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000689 AC: 1 AN: 145164 AF XY: 0.0000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000433

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: 7.17e-7 AC: 1 AN: 1394502 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 687650

African (AFR) AF: 0.00 AC: 0 AN: 31518

American (AMR) AF: 0.0000282 AC: 1 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: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1076940

Other (OTH) AF: 0.00 AC: 0 AN: 57536

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.0025
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.48
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.89	P
Vest4		0.77
MutPred		0.68		Gain of catalytic residue at V186 (P = 0.0223)
MVP		0.49
ClinPred		0.70	D
GERP RS		4.3
Varity_R		0.55
gMVP		0.75
Mutation Taster		=81/19	polymorphism

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: rs1188310365; hg19: chr7-76141126;