rs9381199

chr6-42594234-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001363705.2(UBR2):c.461C>T(p.Thr154Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, UBR2
• BP4: Computational evidence support a benign effect (MetaRNN=0.16270658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR2	NM_001363705.2	c.461C>T	p.Thr154Ile	missense_variant	4/47	ENST00000372901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR2	ENST00000372901.2	c.461C>T	p.Thr154Ile	missense_variant	4/47	5	NM_001363705.2	P3
UBR2	ENST00000372899.6	c.461C>T	p.Thr154Ile	missense_variant	4/47	1		A1
UBR2	ENST00000372903.6	c.461C>T	p.Thr154Ile	missense_variant	4/12	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461132 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0094	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.84	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.23
MutPred		0.43		Loss of disorder (P = 0.0562);Loss of disorder (P = 0.0562);Loss of disorder (P = 0.0562);
MVP		0.24
MPC		0.44
ClinPred		0.49	T
GERP RS		4.5
Varity_R		0.20
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs9381199; hg19: chr6-42561972;