Variant 3-33425667-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_014517.5(UBP1):c.188C>G(p.Pro63Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000879 in 1,603,360 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 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 0 hom. )

Consequence

UBP1
NM_014517.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

UBP1 (HGNC:12507): (upstream binding protein 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, UBP1

BP4

Computational evidence support a benign effect (MetaRNN=0.13173714).

BS2

High AC in GnomAd at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBP1	NM_014517.5 linkuse as main transcript	c.188C>G	p.Pro63Arg	missense_variant	2/16	ENST00000283629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBP1	ENST00000283629.8 linkuse as main transcript	c.188C>G	p.Pro63Arg	missense_variant	2/16	1	NM_014517.5	P3	Q9NZI7-1

Frequencies

GnomAD3 genomes

AF:

0.000599

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000669

AC:

168

AN:

251194

Hom.:

AF XY:

0.000611

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000908

AC:

1318

AN:

1451342

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

601

AN XY:

721414

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000199

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.000752

GnomAD4 genome

AF:

0.000599

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000802

Hom.:

Bravo

AF:

0.000586

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000774

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.188C>G (p.P63R) alteration is located in exon 2 (coding exon 2) of the UBP1 gene. This alteration results from a C to G substitution at nucleotide position 188, causing the proline (P) at amino acid position 63 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.020

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

L;L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.0

D;D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.98

D;D;D;.

Vest4

0.84

MVP

0.29

MPC

2.1

ClinPred

0.18

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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