Variant chr12-124912791-A-G 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.981T>C(p.Ile327Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 112,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00056 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.688

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=-0.75).

BP6

Variant 12-124912791-A-G is Benign according to our data. Variant chr12-124912791-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1698276.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.688 with no splicing effect.

BS2

High AC in GnomAd4 at 271 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7 linkuse as main transcript	c.981T>C	p.Ile327Ile	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.981T>C	p.Ile327Ile	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.981T>C	p.Ile327Ile	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.451+530T>C		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

270

AN:

112546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000709

Gnomad ASJ

AF:

0.000359

Gnomad EAS

AF:

0.00437

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000529

Gnomad MID

AF:

0.0125

Gnomad NFE

AF:

0.000927

Gnomad OTH

AF:

0.00260

GnomAD3 exomes

AF:

0.00166

AC:

407

AN:

244502

Hom.:

AF XY:

0.00141

AC XY:

187

AN XY:

132664

show subpopulations

Gnomad AFR exome

AF:

0.00463

Gnomad AMR exome

AF:

0.000640

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0146

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000526

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000559

AC:

815

AN:

1457378

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

379

AN XY:

724974

show subpopulations

Gnomad4 AFR exome

AF:

0.00481

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00250

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000424

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00241

AC:

271

AN:

112618

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

120

AN XY:

55084

show subpopulations

Gnomad4 AFR

AF:

0.00674

Gnomad4 AMR

AF:

0.000709

Gnomad4 ASJ

AF:

0.000359

Gnomad4 EAS

AF:

0.00438

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000529

Gnomad4 NFE

AF:

0.000927

Gnomad4 OTH

AF:

0.00257

Alfa

AF:

0.00289

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

GeneDx

Jan 20, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.2

DANN

Benign

0.70

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