Genetic Variant UBB:p.Pro189Pro (chr17-16382474-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_018955.4(UBB):c.567C>T(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBB
NM_018955.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.37

Variant links:

Genes affected

UBB (HGNC:12463): (ubiquitin B) This gene encodes ubiquitin, one of the most conserved proteins known. Ubiquitin has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene consists of three direct repeats of the ubiquitin coding sequence with no spacer sequence. Consequently, the protein is expressed as a polyubiquitin precursor with a final amino acid after the last repeat. An aberrant form of this protein has been detected in patients with Alzheimer's disease and Down syndrome. Pseudogenes of this gene are located on chromosomes 1, 2, 13, and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

UBB links:

ENSG00000265401 (HGNC:):

ENSG00000265401 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-16382474-C-T is Benign according to our data. Variant chr17-16382474-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728567.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.37 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBB	NM_018955.4 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 2 of 2	ENST00000302182.8	NP_061828.1	P0CG47Q5U5U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBB	ENST00000302182.8 link	c.567C>T	p.Pro189Pro	synonymous_variant	Exon 2 of 2	1	NM_018955.4	ENSP00000304697.3		P0CG47

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

456

AN:

115330

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.00305

Gnomad AMR

AF:

0.00359

Gnomad ASJ

AF:

0.000697

Gnomad EAS

AF:

0.00584

Gnomad SAS

AF:

0.00418

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.0400

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00574

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000153

AC:

AN:

1441212

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

717316

show subpopulations

Gnomad4 AFR exome

AF:

0.000154

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000908

Gnomad4 OTH exome

AF:

0.0000850

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00396

AC:

457

AN:

115398

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

228

AN XY:

56464

show subpopulations

Gnomad4 AFR

AF:

0.00602

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.000697

Gnomad4 EAS

AF:

0.00586

Gnomad4 SAS

AF:

0.00448

Gnomad4 FIN

AF:

0.0100

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.0109

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.38

DANN

Benign

0.80

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