chr3-119187797-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006952.4(UPK1B):​c.92C>T​(p.Ala31Val) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,706 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 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

UPK1B
NM_006952.4 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63
Variant links:
Genes affected
UPK1B (HGNC:12578): (uroplakin 1B) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is found in the asymmetrical unit membrane (AUM) where it can form a complex with other transmembrane 4 superfamily proteins. It may play a role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41141564).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UPK1BNM_006952.4 linkc.92C>T p.Ala31Val missense_variant Exon 3 of 8 ENST00000264234.8 NP_008883.2 O75841

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UPK1BENST00000264234.8 linkc.92C>T p.Ala31Val missense_variant Exon 3 of 8 1 NM_006952.4 ENSP00000264234.3 O75841
ENSG00000251012ENST00000490594.2 linkc.236C>T p.Ala79Val missense_variant Exon 2 of 2 3 ENSP00000424708.3 H0Y9P7

Frequencies

GnomAD3 genomes
AF:
0.0000527
AC:
8
AN:
151746
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251364
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461840
Hom.:
0
Cov.:
35
AF XY:
0.0000303
AC XY:
22
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000527
AC:
8
AN:
151866
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74192
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.92C>T (p.A31V) alteration is located in exon 3 (coding exon 2) of the UPK1B gene. This alteration results from a C to T substitution at nucleotide position 92, causing the alanine (A) at amino acid position 31 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.52
.;D;.;T;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.29
T;D;D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.41
T;T;T;T;T
MetaSVM
Uncertain
0.34
D
MutationAssessor
Uncertain
2.2
.;M;.;.;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.49
N;N;N;N;N
REVEL
Uncertain
0.57
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Uncertain
0.0090
.;D;T;T;D
Polyphen
1.0, 1.0
.;D;.;.;D
Vest4
0.84, 0.83
MVP
0.62
MPC
0.28
ClinPred
0.35
T
GERP RS
5.5
Varity_R
0.54
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368350153; hg19: chr3-118906644; COSMIC: COSV51766326; API