rs7959

Variant names:

• chr12-124911891-G-A
• rs7959
• NM_021009.7:c.1881C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-124911891-G-A
• chr12-124911891-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS2

The NM_021009.7(UBC):​c.1881C>T​(p.Pro627Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000352 in 142,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000035 (0 hom., cov: 24)
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 4 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 -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.46 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	NM_021009.7	MANE Select	c.1881C>T	p.Pro627Pro	synonymous	Exon 2 of 2	NP_066289.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBC	ENST00000339647.6	TSL:1 MANE Select	c.1881C>T	p.Pro627Pro	synonymous	Exon 2 of 2	ENSP00000344818.5
	UBC	ENST00000536769.1	TSL:6	c.1881C>T	p.Pro627Pro	synonymous	Exon 1 of 1	ENSP00000441543.1
	UBC	ENST00000538617.5	TSL:5	c.741C>T	p.Pro247Pro	synonymous	Exon 4 of 4	ENSP00000443053.1

Frequencies

GnomAD3 genomes AF: 0.0000352 AC: 5 AN: 142112 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000130

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 Cov.: 46

GnomAD4 genome AF: 0.0000352 AC: 5 AN: 142112 Hom.: 0 Cov.: 24 AF XY: 0.0000434 AC XY: 3 AN XY: 69046

African (AFR) AF: 0.000130 AC: 5 AN: 38550

American (AMR) AF: 0.00 AC: 0 AN: 14084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3342

East Asian (EAS) AF: 0.00 AC: 0 AN: 4890

South Asian (SAS) AF: 0.00 AC: 0 AN: 4258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64386

Other (OTH) AF: 0.00 AC: 0 AN: 1916

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.2
DANN	Benign	0.90
PhyloP100		1.5

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: rs7959; hg19: chr12-125396437;