Variant chr12-124913178-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.594C>T(p.Ala198Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,608,546 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 8 hom. )

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33

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=-0.72).

BP6

Variant 12-124913178-G-A is Benign according to our data. Variant chr12-124913178-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643570.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BS2

High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.594C>T	p.Ala198Ala	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.594C>T	p.Ala198Ala	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.594C>T	p.Ala198Ala	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000541272.1 linkuse as main transcript	c.366C>T	p.Ala122Ala	synonymous_variant	3/3	5		ENSP00000440205.1	F5GXK7
UBC	ENST00000538617.5 linkuse as main transcript	c.451+143C>T		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.000207

AC:

AN:

149806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000386

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

250854

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000178

AC:

259

AN:

1458618

Hom.:

Cov.:

155

AF XY:

0.000186

AC XY:

135

AN XY:

725606

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000488

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000207

AC:

AN:

149928

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

73244

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.0000666

Gnomad4 ASJ

AF:

0.000580

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000386

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000239

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

Feb 01, 2023

UBC: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.4

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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