chr2-169828062-G-T

Variant names:

• chr2-169828062-G-T
• rs761566207
• NM_172070.4:c.545+10G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172070.4(UBR3):​c.545+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000825 in 1,211,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: UBR3 NM_172070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 0 publications found

Genes affected

UBR3 (HGNC:30467): (ubiquitin protein ligase E3 component n-recognin 3) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; sensory perception of smell; and suckling behavior. Predicted to act upstream of or within in utero embryonic development and olfactory behavior. Predicted to be integral component of membrane. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172070.4. 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
	UBR3	NM_172070.4	MANE Select	c.545+10G>T		intron	N/A	NP_742067.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR3	ENST00000272793.11	TSL:5 MANE Select	c.545+10G>T		intron	N/A	ENSP00000272793.5	Q6ZT12-1
	UBR3	ENST00000949146.1		c.545+10G>T		intron	N/A	ENSP00000619205.1
	UBR3	ENST00000949147.1		c.545+10G>T		intron	N/A	ENSP00000619206.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.25e-7 AC: 1 AN: 1211420 Hom.: 0 Cov.: 35 AF XY: 0.00000171 AC XY: 1 AN XY: 585852

⚠️ 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: 24286

American (AMR) AF: 0.00 AC: 0 AN: 14036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17186

East Asian (EAS) AF: 0.00 AC: 0 AN: 27394

South Asian (SAS) AF: 0.00 AC: 0 AN: 56562

European-Finnish (FIN) AF: 0.0000337 AC: 1 AN: 29680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4912

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 987718

Other (OTH) AF: 0.00 AC: 0 AN: 49646

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs761566207; hg19: chr2-170684572;