Genetic Variant UBR7:p.Gly6Ser (chr14-93207307-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071632296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
UBR7	NM_175748.4 link	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 11	ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2 link	n.52G>A		non_coding_transcript_exon_variant	Exon 1 of 10
GON7	NM_032490.5 link	c.-270C>T		upstream_gene_variant		ENST00000306954.5	NP_115879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBR7	ENST00000013070.11 link	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 11	1	NM_175748.4	ENSP00000013070.6	Q8N806
ENSG00000259066	ENST00000557574.1 link	c.208-2517G>A		intron_variant	Intron 2 of 4	4		ENSP00000451369.1	G3V3Q6
GON7	ENST00000306954.5 link	c.-270C>T		upstream_gene_variant		1	NM_032490.5	ENSP00000306320.4	Q9BXV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000627

AC:

AN:

159536

Hom.:

AF XY:

0.0000118

AC XY:

AN XY:

84536

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16G>A (p.G6S) alteration is located in exon 1 (coding exon 1) of the UBR7 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0071

T;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.16

M_CAP

Benign

0.029

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.20

N;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.010

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.24

T;T;D

Sift4G

Benign

0.66

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.079

MutPred

0.12

Gain of glycosylation at G6 (P = 0.0155);Gain of glycosylation at G6 (P = 0.0155);Gain of glycosylation at G6 (P = 0.0155);

MVP

0.45

MPC

0.45

ClinPred

0.088

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.037

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over