Variant chr12-124912149-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021009.7(UBC):c.1623T>C(p.Thr541Thr) 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 0.00048 ( 0 hom., cov: 3)

Exomes 𝑓: 0.0014 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-124912149-A-G is Benign according to our data. Variant chr12-124912149-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 1247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.1623T>C	p.Thr541Thr	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.1623T>C	p.Thr541Thr	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.1623T>C	p.Thr541Thr	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.483T>C	p.Thr161Thr	synonymous_variant	4/4	5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

8266

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000923

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000631

AC:

AN:

107822

Hom.:

AF XY:

0.000797

AC XY:

AN XY:

56492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000511

Gnomad ASJ exome

AF:

0.00435

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.000153

Gnomad FIN exome

AF:

0.000194

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00144

AC:

1247

AN:

863320

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

658

AN XY:

427420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000988

Gnomad4 AMR exome

AF:

0.000355

Gnomad4 ASJ exome

AF:

0.00674

Gnomad4 EAS exome

AF:

0.000332

Gnomad4 SAS exome

AF:

0.000291

Gnomad4 FIN exome

AF:

0.000287

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000476

AC:

AN:

8396

Hom.:

Cov.:

AF XY:

0.000394

AC XY:

AN XY:

5080

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00109

Gnomad4 NFE

AF:

0.000922

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00174

Hom.:

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

-0.74

CADD

Benign

0.056

DANN

Benign

0.43

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