Genetic Variant UPK1B:p.Ala31Val (chr3-119187797-C-T) – ACMG Classification: Uncertain_significance (1 pts)

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

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]

UPK1B links:

ENSG00000251012 (HGNC:):

ENSG00000251012 links:

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
UPK1B	NM_006952.4 link	c.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
UPK1B	ENST00000264234.8 link	c.92C>T	p.Ala31Val	missense_variant	Exon 3 of 8	1	NM_006952.4	ENSP00000264234.3		O75841
ENSG00000251012	ENST00000490594.2 link	c.236C>T	p.Ala79Val	missense_variant	Exon 2 of 2	3		ENSP00000424708.3		H0Y9P7

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151746

Hom.:

Cov.:

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:

AN:

251364

Hom.:

AF XY:

0.0000736

AC XY:

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:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

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:

AN:

151866

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

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.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

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

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

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

LIST_S2

Benign

0.29

T;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.41

T;T;T;T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.2

.;M;.;.;.

PrimateAI

Uncertain

0.64

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over