12-124912791-A-G

Variant names:

• chr12-124912791-A-G
• rs150274132
• NM_021009.7:c.981T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_021009.7(UBC):​c.981T>C​(p.Ile327Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 112,618 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00056 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.688
• Publications: 3 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-124912791-A-G is Benign according to our data. Variant chr12-124912791-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1698276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.688 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.981T>C	p.Ile327Ile	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.981T>C	p.Ile327Ile	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.981T>C	p.Ile327Ile	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.981T>C	p.Ile327Ile	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 270 AN: 112546 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00672

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000709

Gnomad ASJ AF: 0.000359

Gnomad EAS AF: 0.00437

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000529

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.000927

Gnomad OTH AF: 0.00260

GnomAD2 exomes AF: 0.00166 AC: 407 AN: 244502 AF XY: 0.00141

Gnomad AFR exome AF: 0.00463

Gnomad AMR exome AF: 0.000640

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.0146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.000677

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000559 AC: 815 AN: 1457378 Hom.: 5 Cov.: 38 AF XY: 0.000523 AC XY: 379 AN XY: 724974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00481 AC: 159 AN: 33026

American (AMR) AF: 0.000270 AC: 12 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25942

East Asian (EAS) AF: 0.00250 AC: 95 AN: 38056

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86102

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5708

European-Non Finnish (NFE) AF: 0.000424 AC: 471 AN: 1110574

Other (OTH) AF: 0.00112 AC: 67 AN: 60064

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00241 AC: 271 AN: 112618 Hom.: 0 Cov.: 23 AF XY: 0.00218 AC XY: 120 AN XY: 55084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00674 AC: 187 AN: 27752

American (AMR) AF: 0.000709 AC: 8 AN: 11290

Ashkenazi Jewish (ASJ) AF: 0.000359 AC: 1 AN: 2782

East Asian (EAS) AF: 0.00438 AC: 15 AN: 3428

South Asian (SAS) AF: 0.00 AC: 0 AN: 3520

European-Finnish (FIN) AF: 0.000529 AC: 4 AN: 7558

Middle Eastern (MID) AF: 0.0135 AC: 2 AN: 148

European-Non Finnish (NFE) AF: 0.000927 AC: 50 AN: 53954

Other (OTH) AF: 0.00257 AC: 4 AN: 1558

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00289 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs150274132; hg19: chr12-125397337;