7-76510821-G-A

Variant names:

• chr7-76510821-G-A
• rs201668989
• NM_001347684.2:c.86-82G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001347684.2(UPK3B):​c.86-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 152,166 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3B NM_001347684.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010082185).
• BP6: Variant 7-76510821-G-A is Benign according to our data. Variant chr7-76510821-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2295480.Status of the report is criteria_provided_single_submitter, 1 stars.

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.86-82G>A		intron	N/A	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.86-82G>A		intron	N/A	ENSP00000334938.3	Q9BT76-3
	UPK3B	ENST00000257632.9	TSL:2	c.169G>A	p.Ala57Thr	missense	Exon 1 of 4	ENSP00000257632.5	Q9BT76-1
	UPK3B	ENST00000911147.1		c.86-82G>A		intron	N/A	ENSP00000581206.1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000144 AC: 33 AN: 228958 AF XY: 0.000144

Gnomad AFR exome AF: 0.000572

Gnomad AMR exome AF: 0.000153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000176

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000986

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000144 AC: 208 AN: 1448536 Hom.: 1 Cov.: 31 AF XY: 0.000146 AC XY: 105 AN XY: 719026

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000331 AC: 11 AN: 33214

American (AMR) AF: 0.000138 AC: 6 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.000332 AC: 13 AN: 39118

South Asian (SAS) AF: 0.000318 AC: 27 AN: 85032

European-Finnish (FIN) AF: 0.0000386 AC: 2 AN: 51814

Middle Eastern (MID) AF: 0.000545 AC: 3 AN: 5500

European-Non Finnish (NFE) AF: 0.000123 AC: 136 AN: 1104854

Other (OTH) AF: 0.000167 AC: 10 AN: 59708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74410

African (AFR) AF: 0.000385 AC: 16 AN: 41526

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000367 Hom.: 0

Bravo AF: 0.000246

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000234 AC: 2

ExAC AF: 0.000174 AC: 21

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.072
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.32
DANN	Benign	0.78
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.0050
Sift	Benign	0.34	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.027
MVP		0.067
ClinPred		0.0055	T
GERP RS		-4.6
PromoterAI		0.036	Neutral
Varity_R		0.032
Mutation Taster		=99/1	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: rs201668989; hg19: chr7-76140138; COSMIC: COSV107237356; COSMIC: COSV107237356;