Variant 12-124912884-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021009.7(UBC):c.888C>T(p.His296His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,610,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.106

Variant links:

Genes affected

UBC (HGNC:12468): (ubiquitin C) This gene represents a ubiquitin gene, ubiquitin C. The encoded protein is a polyubiquitin precursor. Conjugation of ubiquitin monomers or polymers can lead to various effects within a cell, depending on the residues to which ubiquitin is conjugated. Ubiquitination has been associated with protein degradation, DNA repair, cell cycle regulation, kinase modification, endocytosis, and regulation of other cell signaling pathways. [provided by RefSeq, Aug 2010]

UBC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-124912884-G-A is Benign according to our data. Variant chr12-124912884-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643569.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.106 with no splicing effect.

BS2

High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.888C>T	p.His296His	synonymous_variant	2/2	ENST00000339647.6	NP_066289.3	P0CG48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBC	ENST00000339647.6 linkuse as main transcript	c.888C>T	p.His296His	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.888C>T	p.His296His	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.451+437C>T		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

211

AN:

149712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000369

Gnomad AMI

AF:

0.0122

Gnomad AMR

AF:

0.00133

Gnomad ASJ

AF:

0.00667

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.000388

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00192

Gnomad OTH

AF:

0.00386

GnomAD3 exomes

AF:

0.00149

AC:

375

AN:

250996

Hom.:

AF XY:

0.00165

AC XY:

224

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00180

AC:

2632

AN:

1461070

Hom.:

Cov.:

154

AF XY:

0.00184

AC XY:

1340

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000583

Gnomad4 ASJ exome

AF:

0.00884

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00199

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00141

AC:

211

AN:

149832

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

73150

show subpopulations

Gnomad4 AFR

AF:

0.000368

Gnomad4 AMR

AF:

0.00133

Gnomad4 ASJ

AF:

0.00667

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000214

Gnomad4 FIN

AF:

0.000388

Gnomad4 NFE

AF:

0.00192

Gnomad4 OTH

AF:

0.00382

Alfa

AF:

0.00288

Hom.:

EpiCase

AF:

0.00273

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

UBC: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.0

DANN

Benign

0.89

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