Variant chr12-124912515-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021009.7(UBC):c.1257C>T(p.Asp419Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,155,828 control chromosomes in the GnomAD database, including 146,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 1241 hom., cov: 5)

Exomes 𝑓: 0.55 ( 146306 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.218

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 12-124912515-G-A is Benign according to our data. Variant chr12-124912515-G-A is described in ClinVar as [Benign]. Clinvar id is 768598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.218 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.1257C>T	p.Asp419Asp	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.1257C>T	p.Asp419Asp	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.1257C>T	p.Asp419Asp	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.452-335C>T		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

7288

AN:

19628

Hom.:

1241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.508

AC:

121638

AN:

239638

Hom.:

27625

AF XY:

0.526

AC XY:

68215

AN XY:

129584

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.600

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.548

AC:

633607

AN:

1155828

Hom.:

146306

Cov.:

AF XY:

0.552

AC XY:

322968

AN XY:

585496

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.504

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.370

AC:

7304

AN:

19744

Hom.:

1241

Cov.:

AF XY:

0.375

AC XY:

3895

AN XY:

10380

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.443

Hom.:

981

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 28, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.94

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