Variant 12-124912818-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.954T>C(p.Thr318Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,584,808 control chromosomes in the GnomAD database, including 426,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 19345 hom., cov: 22)

Exomes 𝑓: 0.74 ( 407454 hom. )

Consequence

UBC
NM_021009.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0420

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=-0.91).

BP6

Variant 12-124912818-A-G is Benign according to our data. Variant chr12-124912818-A-G is described in ClinVar as [Benign]. Clinvar id is 1335819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.042 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 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.954T>C	p.Thr318Thr	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.954T>C	p.Thr318Thr	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5	P0CG48
UBC	ENST00000536769.1 linkuse as main transcript	c.954T>C	p.Thr318Thr	synonymous_variant	1/1	6		ENSP00000441543.1	P0CG48
UBC	ENST00000538617.5 linkuse as main transcript	c.451+503T>C		intron_variant		5		ENSP00000443053.1	Q96C32

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

71244

AN:

132162

Hom.:

19342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.658

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.569

GnomAD3 exomes

AF:

0.617

AC:

153458

AN:

248818

Hom.:

48849

AF XY:

0.639

AC XY:

86002

AN XY:

134520

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.738

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.738

AC:

1071480

AN:

1452542

Hom.:

407454

Cov.:

136

AF XY:

0.740

AC XY:

534881

AN XY:

722704

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.731

Gnomad4 FIN exome

AF:

0.649

Gnomad4 NFE exome

AF:

0.790

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.539

AC:

71254

AN:

132266

Hom.:

19345

Cov.:

AF XY:

0.540

AC XY:

35008

AN XY:

64826

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.673

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.658

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.684

Hom.:

10527

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

-0.91

CADD

Benign

4.9

DANN

Benign

0.40

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