12-124912335-A-G

Position:

• chr12-124912335-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021009.7(UBC):​c.1437T>C​(p.Ile479Ile) 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0070 (71 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.111

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-124912335-A-G is Benign according to our data. Variant chr12-124912335-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 776775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7	c.1437T>C	p.Ile479Ile	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.1437T>C	p.Ile479Ile	synonymous_variant	2/2	1	NM_021009.7	ENSP00000344818.5
UBC	ENST00000536769.1	c.1437T>C	p.Ile479Ile	synonymous_variant	1/1	6		ENSP00000441543.1
UBC	ENST00000538617.5	c.452-155T>C		intron_variant		5		ENSP00000443053.1

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 78 AN: 2730 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.145

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0500

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0357

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00700 AC: 1008 AN: 144004 Hom.: 71 Cov.: 4 AF XY: 0.00600 AC XY: 480 AN XY: 80026

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.00781

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.00270

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0323 AC: 90 AN: 2788 Hom.: 1 Cov.: 0 AF XY: 0.0339 AC XY: 56 AN XY: 1652

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0500

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00329

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0333

Alfa AF: 0.0593 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.4
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs1071745; hg19: chr12-125396881;