chr6-42605846-C-T

Variant names:

• chr6-42605846-C-T
• NM_001363705.2:c.788C>T

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.788C>T​(p.Thr263Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 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]

ENSG00000310435 (HGNC:):

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=0.24243924).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	NM_001363705.2	MANE Select	c.788C>T	p.Thr263Ile	missense	Exon 6 of 47	NP_001350634.1	Q8IWV8-4
	UBR2	NM_015255.3		c.788C>T	p.Thr263Ile	missense	Exon 6 of 47	NP_056070.1	Q8IWV8-1
	UBR2	NM_001184801.2		c.788C>T	p.Thr263Ile	missense	Exon 6 of 12	NP_001171730.1	Q8IWV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.788C>T	p.Thr263Ile	missense	Exon 6 of 47	ENSP00000361992.1	Q8IWV8-4
	UBR2	ENST00000372899.6	TSL:1	c.788C>T	p.Thr263Ile	missense	Exon 6 of 47	ENSP00000361990.1	Q8IWV8-1
	UBR2	ENST00000372903.6	TSL:1	c.788C>T	p.Thr263Ile	missense	Exon 6 of 12	ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.060	N
PhyloP100		6.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.19
Sift	Benign	0.035	D
Sift4G	Benign	0.25	T
Polyphen		0.11	B
Vest4		0.55
MutPred		0.51		Loss of phosphorylation at T263 (P = 0.0641)
MVP		0.19
MPC		0.51
ClinPred		0.86	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.38
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr6-42573584;