12-124911879-G-C

Variant names:

• chr12-124911879-G-C
• rs1071771
• NM_021009.7:c.1893C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021009.7(UBC):​c.1893C>G​(p.Ile631Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,014 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I631I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UBC NM_021009.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1893C>G	p.Ile631Met	missense	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.1893C>G	p.Ile631Met	missense	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.1893C>G	p.Ile631Met	missense	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.1893C>G	p.Ile631Met	missense	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459014 Hom.: 0 Cov.: 47 AF XY: 0.00000138 AC XY: 1 AN XY: 725742

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110120

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	0.0060	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.044
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.50
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.97	N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.74		Loss of helix (P = 0.0376)
MVP		0.68
MPC		2.8
ClinPred		0.69	D
GERP RS		-2.1
Varity_R		0.14
gMVP		0.91
Mutation Taster		=62/38	polymorphism

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: rs1071771; hg19: chr12-125396425;