rs1175504163

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175748.4(UBR7):c.16G>A(p.Gly6Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBR7
NM_175748.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Publications

0 publications found

Variant links:

Genes affected

UBR7 (HGNC:20344): (ubiquitin protein ligase E3 component n-recognin 7) This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

UBR7 links:

ENSG00000259066 (HGNC:):

ENSG00000259066 links:

GON7 (HGNC:20356): (GON7 subunit of KEOPS complex) Located in cytosol; nucleolus; and nucleoplasm. Part of EKC/KEOPS complex. [provided by Alliance of Genome Resources, Apr 2022]

GON7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.071632296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR7	NM_175748.4	MANE Select	c.16G>A	p.Gly6Ser	missense	Exon 1 of 11	NP_786924.2	Q8N806
UBR7	NR_038150.2		n.52G>A		non_coding_transcript_exon	Exon 1 of 10
GON7	NM_032490.5	MANE Select	c.-270C>T		upstream_gene	N/A	NP_115879.2	Q9BXV9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR7	ENST00000013070.11	TSL:1 MANE Select	c.16G>A	p.Gly6Ser	missense	Exon 1 of 11	ENSP00000013070.6	Q8N806
ENSG00000259066	ENST00000557574.1	TSL:4	c.208-2517G>A		intron	N/A	ENSP00000451369.1	G3V3Q6
UBR7	ENST00000966805.1		c.16G>A	p.Gly6Ser	missense	Exon 1 of 11	ENSP00000636864.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000627

AC:

AN:

159536

AF XY:

0.0000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000828

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.12e-7

AC:

AN:

1404054

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31882

American (AMR)

AF:

0.00

AC:

AN:

36386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25206

East Asian (EAS)

AF:

0.0000276

AC:

AN:

36274

South Asian (SAS)

AF:

0.00

AC:

AN:

79736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081682

Other (OTH)

AF:

0.00

AC:

AN:

58138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.16

M_CAP

Benign

0.029

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.20

PhyloP100

1.5

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.010

REVEL

Benign

0.16

Sift

Benign

0.24

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.079

MutPred

0.12

Gain of glycosylation at G6 (P = 0.0155)

MVP

0.45

MPC

0.45

ClinPred

0.088

GERP RS

1.8

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.037

gMVP

0.40

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over