Variant 12-124912107-A-G 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.1665T>C(p.Ile555Ile) 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 0.080 ( 16 hom., cov: 2)

Exomes 𝑓: 0.057 ( 1292 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0780

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 -21 ACMG points.

BP4

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

BP6

Variant 12-124912107-A-G is Benign according to our data. Variant chr12-124912107-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 774905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.078 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 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.1665T>C	p.Ile555Ile	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.1665T>C	p.Ile555Ile	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.1665T>C	p.Ile555Ile	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.525T>C	p.Ile175Ile	synonymous_variant	4/4	5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.0780

AC:

539

AN:

6906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0820

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0917

Gnomad FIN

AF:

0.0493

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.0867

GnomAD3 exomes

AF:

0.0703

AC:

9027

AN:

128330

Hom.:

492

AF XY:

0.0730

AC XY:

5126

AN XY:

70244

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0224

Gnomad SAS exome

AF:

0.0772

Gnomad FIN exome

AF:

0.0343

Gnomad NFE exome

AF:

0.0772

Gnomad OTH exome

AF:

0.0875

GnomAD4 exome

AF:

0.0570

AC:

50994

AN:

894298

Hom.:

1292

Cov.:

AF XY:

0.0576

AC XY:

25528

AN XY:

442948

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.0490

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.0145

Gnomad4 SAS exome

AF:

0.0643

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0548

Gnomad4 OTH exome

AF:

0.0685

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0797

AC:

559

AN:

7010

Hom.:

Cov.:

AF XY:

0.0824

AC XY:

320

AN XY:

3884

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.0807

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0833

Gnomad4 FIN

AF:

0.0493

Gnomad4 NFE

AF:

0.0533

Gnomad4 OTH

AF:

0.0823

Alfa

AF:

0.0390

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.78

DANN

Benign

0.42

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