Variant 12-124913199-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021009.7(UBC):c.573T>C(p.Asp191Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,454,276 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00063 ( 31 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.153

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-124913199-A-G is Benign according to our data. Variant chr12-124913199-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643572.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000632 (919/1454276) while in subpopulation EAS AF= 0.0183 (711/38922). AF 95% confidence interval is 0.0172. There are 31 homozygotes in gnomad4_exome. There are 469 alleles in male gnomad4_exome subpopulation. Median coverage is 153. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 919 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.573T>C	p.Asp191Asp	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.573T>C	p.Asp191Asp	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.573T>C	p.Asp191Asp	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000541272.1 linkuse as main transcript	c.345T>C	p.Asp115Asp	synonymous_variant	3/3	5		ENSP00000440205.1	F5GXK7
UBC	ENST00000538617.5 linkuse as main transcript	c.451+122T>C		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

472

AN:

122510

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.00292

Gnomad AMR

AF:

0.00260

Gnomad ASJ

AF:

0.00207

Gnomad EAS

AF:

0.0238

Gnomad SAS

AF:

0.00337

Gnomad FIN

AF:

0.00191

Gnomad MID

AF:

0.0181

Gnomad NFE

AF:

0.00183

Gnomad OTH

AF:

0.00467

GnomAD3 exomes

AF:

0.000516

AC:

128

AN:

248298

Hom.:

AF XY:

0.000514

AC XY:

AN XY:

134262

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00546

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000534

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000632

AC:

919

AN:

1454276

Hom.:

Cov.:

153

AF XY:

0.000648

AC XY:

469

AN XY:

723426

show subpopulations

Gnomad4 AFR exome

AF:

0.00175

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.0000771

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000515

Gnomad4 OTH exome

AF:

0.000884

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00383

AC:

470

AN:

122622

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

232

AN XY:

60268

show subpopulations

Gnomad4 AFR

AF:

0.00603

Gnomad4 AMR

AF:

0.00260

Gnomad4 ASJ

AF:

0.00207

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.00338

Gnomad4 FIN

AF:

0.00191

Gnomad4 NFE

AF:

0.00183

Gnomad4 OTH

AF:

0.00462

Alfa

AF:

0.00203

Hom.:

EpiCase

AF:

0.000220

EpiControl

AF:

0.000180

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

-0.81

CADD

Benign

5.9

DANN

Benign

0.58

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