12-124912818-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_021009.7(UBC):​c.954T>A​(p.Thr318Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T318T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 22)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.

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>A	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>A	p.Thr318Thr	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.954T>A	p.Thr318Thr	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.954T>A	p.Thr318Thr	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 132622 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.88e-7 AC: 1 AN: 1452642 Hom.: 0 Cov.: 136 AF XY: 0.00 AC XY: 0 AN XY: 722766

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 85624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105002

Other (OTH) AF: 0.0000167 AC: 1 AN: 59808

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 132728 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 65032

African (AFR) AF: 0.00 AC: 0 AN: 36196

American (AMR) AF: 0.00 AC: 0 AN: 13720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3120

East Asian (EAS) AF: 0.00 AC: 0 AN: 4372

South Asian (SAS) AF: 0.00 AC: 0 AN: 4006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58970

Other (OTH) AF: 0.00 AC: 0 AN: 1848

Alfa AF: 0.00 Hom.: 10527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.41
PhyloP100		0.042

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: COSV108181495; COSMIC: COSV108181495;