dbSNP rs1429218989: UPK3BL1:p.Thr250Asn (chr7-102637568-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001114403.3(UPK3BL1):c.749C>A(p.Thr250Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UPK3BL1
NM_001114403.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00400

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04559478).

BP6

Variant 7-102637568-G-T is Benign according to our data. Variant chr7-102637568-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3331161.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3BL1	NM_001114403.3 link	c.749C>A	p.Thr250Asn	missense_variant	Exon 6 of 6	ENST00000340457.8	NP_001107875.1	B0FP48E5RIL1
POLR2J2-UPK3BL1	NR_173352.1 link	n.1101C>A		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UPK3BL1	ENST00000340457.8 link	c.749C>A	p.Thr250Asn	missense_variant	Exon 6 of 6	1	NM_001114403.3	ENSP00000342938.8	B0FP48
ENSG00000267645	ENST00000476151.5 link	n.*691C>A		non_coding_transcript_exon_variant	Exon 9 of 9	1		ENSP00000418603.1
ENSG00000267645	ENST00000476151.5 link	n.*691C>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000418603.1
ENSG00000205236	ENST00000519541.1 link	n.683+1146C>A		intron_variant	Intron 5 of 25	2		ENSP00000429397.1	A0A286YEE6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

107304

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000932

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: AS_VQSR

AF:

0.00000494

AC:

AN:

404714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

212206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000850

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:

0.00000411

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000280

AC:

AN:

107304

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

50334

show subpopulations

Gnomad4 AFR

AF:

0.0000932

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

Alfa

AF:

0.000337

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 11, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.3

DANN

Benign

0.79

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0034

M_CAP

Benign

0.075

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.050

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.25

REVEL

Benign

0.031

Sift

Benign

0.76

Sift4G

Benign

0.70

Vest4

0.059

MutPred

0.17

Loss of glycosylation at T250 (P = 0.0336);

MVP

0.030

ClinPred

0.037

GERP RS

-0.62

Varity_R

0.032

gMVP

0.24

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

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