14-93209909-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_175748.4(UBR7):c.236G>C(p.Ser79Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

UBR7
NM_175748.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000342 (50/1461778) while in subpopulation NFE AF= 0.0000441 (49/1111964). AF 95% confidence interval is 0.0000337. There are 0 homozygotes in gnomad4_exome. There are 22 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR7	NM_175748.4 link	c.236G>C	p.Ser79Thr	missense_variant	Exon 2 of 11	ENST00000013070.11	NP_786924.2
UBR7	NR_038150.2 link	n.187-739G>C		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR7	ENST00000013070.11 link	c.236G>C	p.Ser79Thr	missense_variant	Exon 2 of 11	1	NM_175748.4	ENSP00000013070.6		Q8N806
ENSG00000259066	ENST00000557574.1 link	c.293G>C	p.Ser98Thr	missense_variant	Exon 3 of 5	4		ENSP00000451369.1		G3V3Q6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251442

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236G>C (p.S79T) alteration is located in exon 2 (coding exon 2) of the UBR7 gene. This alteration results from a G to C substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a threonine (T). 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

0.32

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

.;D;D

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.78

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Uncertain

-0.019

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

N;D;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.098

T;D;D

Polyphen

0.99

.;D;.

Vest4

0.53

MutPred

0.72

.;Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.73

MPC

1.1

ClinPred

0.88

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.54

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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