Genetic Variant UPK3BL1:p.Glu171Gln (chr7-102639174-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114403.3(UPK3BL1):c.511G>C(p.Glu171Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 50)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UPK3BL1
NM_001114403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.303

Variant links:

Genes affected

UPK3BL1 (HGNC:37278): (uroplakin 3B like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

UPK3BL1 links:

ENSG00000267645 (HGNC:):

ENSG00000267645 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.064394325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3BL1	NM_001114403.3 link	c.511G>C	p.Glu171Gln	missense_variant	Exon 4 of 6	ENST00000340457.8	NP_001107875.1	B0FP48E5RIL1
POLR2J2-UPK3BL1	NR_173352.1 link	n.863G>C		non_coding_transcript_exon_variant	Exon 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UPK3BL1	ENST00000340457.8 link	c.511G>C	p.Glu171Gln	missense_variant	Exon 4 of 6	1	NM_001114403.3	ENSP00000342938.8	B0FP48
ENSG00000267645	ENST00000476151.5 link	n.*453G>C		non_coding_transcript_exon_variant	Exon 7 of 9	1		ENSP00000418603.1
ENSG00000205236	ENST00000519541.1 link	n.511G>C		non_coding_transcript_exon_variant	Exon 4 of 26	2		ENSP00000429397.1	A0A286YEE6
ENSG00000267645	ENST00000476151.5 link	n.*453G>C		3_prime_UTR_variant	Exon 7 of 9	1		ENSP00000418603.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150706

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1379448

Hom.:

Cov.:

125

AF XY:

0.00

AC XY:

AN XY:

680650

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73560

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>C (p.E171Q) alteration is located in exon 4 (coding exon 4) of the UPK3BL gene. This alteration results from a G to C substitution at nucleotide position 511, causing the glutamic acid (E) at amino acid position 171 to be replaced by a glutamine (Q). 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

Benign

0.083

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.2

DANN

Benign

0.85

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0051

M_CAP

Benign

0.083

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.090

REVEL

Benign

0.033

Sift

Benign

0.37

Sift4G

Benign

0.34

Vest4

0.093

MutPred

0.20

Loss of sheet (P = 0.0817);

MVP

0.014

ClinPred

0.017

GERP RS

-0.24

Varity_R

0.037

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over