Genetic Variant UBC:p.Thr546Thr (chr12-124912134-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_021009.7(UBC):c.1638T>C(p.Thr546Thr) 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 0.0020 ( 0 hom., cov: 3)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.333

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=-0.73).

BP6

Variant 12-124912134-A-G is Benign according to our data. Variant chr12-124912134-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3770733.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.333 with no splicing effect.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBC	NM_021009.7 link	c.1638T>C	p.Thr546Thr	synonymous_variant	Exon 2 of 2	ENST00000339647.6	NP_066289.3	P0CG48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBC	ENST00000339647.6 link	c.1638T>C	p.Thr546Thr	synonymous_variant	Exon 2 of 2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 link	c.1638T>C	p.Thr546Thr	synonymous_variant	Exon 1 of 1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 link	c.498T>C	p.Thr166Thr	synonymous_variant	Exon 4 of 4	5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

AN:

6798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000734

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:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000477

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000224

AC:

AN:

98286

Hom.:

AF XY:

0.000151

AC XY:

AN XY:

52990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000617

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000441

Gnomad NFE exome

AF:

0.000418

Gnomad OTH exome

AF:

0.000457

GnomAD4 exome

AF:

0.000456

AC:

392

AN:

858724

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

219

AN XY:

425688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000128

Gnomad4 ASJ exome

AF:

0.000561

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.00469

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000419

GnomAD4 genome

AF:

0.00202

AC:

AN:

6914

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

AN XY:

4126

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00549

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.000476

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00910

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UBC: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.4

DANN

Benign

0.45

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