6-42659696-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001363705.2(UBR2):​c.3283G>T​(p.Ala1095Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1095P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060635686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.3283G>T	p.Ala1095Ser	missense_variant	Exon 30 of 47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.3283G>T	p.Ala1095Ser	missense_variant	Exon 30 of 47	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.3283G>T	p.Ala1095Ser	missense_variant	Exon 30 of 47	1		ENSP00000361990.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.8
DANN	Benign	0.91
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.62	N;N
REVEL	Benign	0.058
Sift	Benign	0.41	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.010	B;B
Vest4		0.081
MutPred		0.079		Gain of disorder (P = 0.0435);Gain of disorder (P = 0.0435);
MVP		0.21
MPC		0.37
ClinPred		0.080	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.015
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs6917033; hg19: chr6-42627434;