NM_001363705.2:c.3283G>C

Variant names:

• chr6-42659696-G-C
• rs6917033
• NM_001363705.2:c.3283G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363705.2(UBR2):​c.3283G>C​(p.Ala1095Pro) variant causes a missense 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. 16/22 in silico tools predict 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: 30)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 28 publications found

Genes affected

UBR2 (HGNC:21289): (ubiquitin protein ligase E3 component n-recognin 2) Enables leucine binding activity. Involved in cellular response to leucine and negative regulation of TOR signaling. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. Predicted to colocalize with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10587889).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363705.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	NM_001363705.2	MANE Select	c.3283G>C	p.Ala1095Pro	missense	Exon 30 of 47	NP_001350634.1
	UBR2	NM_015255.3		c.3283G>C	p.Ala1095Pro	missense	Exon 30 of 47	NP_056070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.3283G>C	p.Ala1095Pro	missense	Exon 30 of 47	ENSP00000361992.1
	UBR2	ENST00000372899.6	TSL:1	c.3283G>C	p.Ala1095Pro	missense	Exon 30 of 47	ENSP00000361990.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.057
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.084	B
Vest4		0.35
MutPred		0.10		Gain of glycosylation at A1095 (P = 0.0259)
MVP		0.16
MPC		0.53
ClinPred		0.16	T
GERP RS		2.8
Varity_R		0.047
gMVP		0.36
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6917033; hg19: chr6-42627434;