7-76510762-C-A

Variant names:

• chr7-76510762-C-A
• NM_001347684.2:c.85+25C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001347684.2(UPK3B):​c.85+25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UPK3B NM_001347684.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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]

LOC124901675 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06579825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3B	NM_001347684.2	c.85+25C>A		intron_variant	Intron 1 of 5	ENST00000334348.8	NP_001334613.1
LOC124901675	XR_007060388.1	n.-29G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK3B	ENST00000334348.8	c.85+25C>A		intron_variant	Intron 1 of 5	2	NM_001347684.2	ENSP00000334938.3
UPK3B	ENST00000257632.9	c.110C>A	p.Ala37Glu	missense_variant	Exon 1 of 4	2		ENSP00000257632.5
UPK3B	ENST00000394849.1	c.85+25C>A		intron_variant	Intron 1 of 4	2		ENSP00000378319.1
UPK3B	ENST00000490360.1	n.8C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405372 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 691954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.9
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.034	D
Polyphen		0.67	P
Vest4		0.095
MutPred		0.27		Gain of solvent accessibility (P = 0.005);
MVP		0.014
ClinPred		0.14	T
GERP RS		-5.2
Varity_R		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-76140079;