chr12-124912818-A-G

Variant names:

• chr12-124912818-A-G
• rs8963
• NM_021009.7:c.954T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0420
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021009.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	NM_021009.7	MANE Select	c.954T>C	p.Thr318Thr	synonymous	Exon 2 of 2	NP_066289.3	P0CG48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	ENST00000339647.6	TSL:1 MANE Select	c.954T>C	p.Thr318Thr	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.954T>C	p.Thr318Thr	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.954T>C	p.Thr318Thr	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 71244 AN: 132162 Hom.: 19342 Cov.: 22

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

GnomAD2 exomes AF: 0.617 AC: 153458 AN: 248818 AF XY: 0.639

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 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

African (AFR) AF: 0.242 AC: 8082 AN: 33402

American (AMR) AF: 0.522 AC: 23209 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 18824 AN: 25842

East Asian (EAS) AF: 0.161 AC: 6356 AN: 39528

South Asian (SAS) AF: 0.731 AC: 62555 AN: 85624

European-Finnish (FIN) AF: 0.649 AC: 34563 AN: 53246

Middle Eastern (MID) AF: 0.746 AC: 4261 AN: 5710

European-Non Finnish (NFE) AF: 0.790 AC: 872543 AN: 1104966

Other (OTH) AF: 0.687 AC: 41087 AN: 59798

GnomAD4 genome AF: 0.539 AC: 71254 AN: 132266 Hom.: 19345 Cov.: 22 AF XY: 0.540 AC XY: 35008 AN XY: 64826

African (AFR) AF: 0.265 AC: 9539 AN: 36000

American (AMR) AF: 0.563 AC: 7697 AN: 13662

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2099 AN: 3118

East Asian (EAS) AF: 0.188 AC: 820 AN: 4354

South Asian (SAS) AF: 0.658 AC: 2624 AN: 3990

European-Finnish (FIN) AF: 0.589 AC: 5557 AN: 9436

Middle Eastern (MID) AF: 0.606 AC: 143 AN: 236

European-Non Finnish (NFE) AF: 0.701 AC: 41251 AN: 58846

Other (OTH) AF: 0.569 AC: 1048 AN: 1842

Alfa AF: 0.684 Hom.: 10527

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.40
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8963; hg19: chr12-125397364; COSMIC: COSV60058166; COSMIC: COSV60058166;