chr12-124912240-G-A

Position:

• chr12-124912240-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_021009.7(UBC):​c.1532C>T​(p.Thr511Ile) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.48

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBC	NM_021009.7	c.1532C>T	p.Thr511Ile	missense_variant	2/2	ENST00000339647.6	NP_066289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBC	ENST00000339647.6	c.1532C>T	p.Thr511Ile	missense_variant	2/2	1	NM_021009.7	ENSP00000344818.5
UBC	ENST00000536769.1	c.1532C>T	p.Thr511Ile	missense_variant	1/1	6		ENSP00000441543.1
UBC	ENST00000538617.5	c.452-60C>T		intron_variant		5		ENSP00000443053.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000412 AC: 2 AN: 48556 Hom.: 0 Cov.: 0 AF XY: 0.0000667 AC XY: 2 AN XY: 29976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000983

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.1532C>T (p.T511I) alteration is located in exon 2 (coding exon 1) of the UBC gene. This alteration results from a C to T substitution at nucleotide position 1532, causing the threonine (T) at amino acid position 511 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.2	N;N
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.50	P;P
Vest4		0.53
MutPred		0.62		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.93
MPC		2.8
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.18
gMVP		0.39

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: chr12-125396786;