rs79404795

Variant names:

• chr12-124912134-A-G
• rs79404795
• NM_021009.7:c.1638T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-124912134-A-G
• chr12-124912134-A-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_021009.7(UBC):​c.1638T>C​(p.Thr546Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0020 (0 hom., cov: 3)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: UBC NM_021009.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.333
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-124912134-A-G is Benign according to our data. Variant chr12-124912134-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3770733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.333 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.1638T>C	p.Thr546Thr	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.1638T>C	p.Thr546Thr	synonymous	Exon 2 of 2	ENSP00000344818.5	P0CG48
	UBC	ENST00000536769.1	TSL:6	c.1638T>C	p.Thr546Thr	synonymous	Exon 1 of 1	ENSP00000441543.1	P0CG48
	UBC	ENST00000874892.1		c.1638T>C	p.Thr546Thr	synonymous	Exon 2 of 2	ENSP00000544951.1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 12 AN: 6798 Hom.: 0 Cov.: 3

Gnomad AFR AF: 0.000734

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: 0.00894

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000477

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000224 AC: 22 AN: 98286 AF XY: 0.000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000617

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000441

Gnomad NFE exome AF: 0.000418

Gnomad OTH exome AF: 0.000457

GnomAD4 exome AF: 0.000456 AC: 392 AN: 858724 Hom.: 0 Cov.: 13 AF XY: 0.000514 AC XY: 219 AN XY: 425688

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

African (AFR) AF: 0.00 AC: 0 AN: 19866

American (AMR) AF: 0.000128 AC: 4 AN: 31302

Ashkenazi Jewish (ASJ) AF: 0.000561 AC: 8 AN: 14272

East Asian (EAS) AF: 0.00 AC: 0 AN: 23116

South Asian (SAS) AF: 0.000256 AC: 10 AN: 39024

European-Finnish (FIN) AF: 0.00469 AC: 160 AN: 34110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2232

European-Non Finnish (NFE) AF: 0.000296 AC: 196 AN: 661402

Other (OTH) AF: 0.000419 AC: 14 AN: 33400

⚠️ 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: 0.00202 AC: 14 AN: 6914 Hom.: 0 Cov.: 3 AF XY: 0.00267 AC XY: 11 AN XY: 4126

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

African (AFR) AF: 0.00139 AC: 2 AN: 1438

American (AMR) AF: 0.00 AC: 0 AN: 1402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 92

East Asian (EAS) AF: 0.00 AC: 0 AN: 332

South Asian (SAS) AF: 0.00549 AC: 1 AN: 182

European-Finnish (FIN) AF: 0.00894 AC: 10 AN: 1118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.000476 AC: 1 AN: 2100

Other (OTH) AF: 0.00 AC: 0 AN: 162

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000550246), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00910 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.4
DANN	Benign	0.45
PhyloP100		0.33
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: rs79404795; hg19: chr12-125396680;