12-124912791-A-T

Variant names:

• chr12-124912791-A-T
• NM_021009.7:c.981T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021009.7(UBC):​c.981T>A​(p.Ile327Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I327I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=0.688 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBC	NM_021009.7	c.981T>A	p.Ile327Ile	synonymous_variant	Exon 2 of 2	ENST00000339647.6	NP_066289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBC	ENST00000339647.6	c.981T>A	p.Ile327Ile	synonymous_variant	Exon 2 of 2	1	NM_021009.7	ENSP00000344818.5
UBC	ENST00000536769.1	c.981T>A	p.Ile327Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000441543.1
UBC	ENST00000538617.5	c.451+530T>A		intron_variant	Intron 3 of 3	5		ENSP00000443053.1
UBC	ENST00000541272.1	c.*244T>A		downstream_gene_variant		5		ENSP00000440205.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-125397337;