12-124911942-T-C

Position:

• chr12-124911942-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_021009.7(UBC):​c.1830A>G​(p.Gln610Gln) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (25163 hom., cov: 17)
  • Exomes 𝑓: 0.77 (428748 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.598

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-124911942-T-C is Benign according to our data. Variant chr12-124911942-T-C is described in ClinVar as [Benign]. Clinvar id is 768597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.598 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7	c.1830A>G	p.Gln610Gln	synonymous_variant	2/2	ENST00000339647.6	NP_066289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBC	ENST00000339647.6	c.1830A>G	p.Gln610Gln	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5
UBC	ENST00000536769.1	c.1830A>G	p.Gln610Gln	synonymous_variant	1/1	6		ENSP00000441543.1
UBC	ENST00000538617.5	c.690A>G	p.Gln230Gln	synonymous_variant	4/4	5		ENSP00000443053.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 76796 AN: 125442 Hom.: 25150 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.754

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.627

GnomAD3 exomes AF: 0.690 AC: 157790 AN: 228794 Hom.: 59778 AF XY: 0.707 AC XY: 87920 AN XY: 124316

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.768

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.766

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.723

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.771 AC: 1063272 AN: 1378414 Hom.: 428748 Cov.: 63 AF XY: 0.773 AC XY: 530639 AN XY: 686744

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.822

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.612 AC: 76843 AN: 125560 Hom.: 25163 Cov.: 17 AF XY: 0.601 AC XY: 36611 AN XY: 60952

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.626

Alfa AF: 0.724 Hom.: 6793

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 28, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1071727; hg19: chr12-125396488; COSMIC: COSV60059134; COSMIC: COSV60059134;