Genetic Variant UBR7:p.Ala8Val (chr14-93207314-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_175748.4(UBR7):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 1,405,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

UBR7
NM_175748.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

2 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:

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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=0.13661638).

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.23C>T	p.Ala8Val	missense	Exon 1 of 11	NP_786924.2	Q8N806
UBR7	NR_038150.2		n.59C>T		non_coding_transcript_exon	Exon 1 of 10
GON7	NM_032490.5	MANE Select	c.-277G>A		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.23C>T	p.Ala8Val	missense	Exon 1 of 11	ENSP00000013070.6	Q8N806
ENSG00000259066	ENST00000557574.1	TSL:4	c.208-2510C>T		intron	N/A	ENSP00000451369.1	G3V3Q6
UBR7	ENST00000966805.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 11	ENSP00000636864.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000712

AC:

AN:

1405144

Hom.:

Cov.:

AF XY:

0.00000865

AC XY:

AN XY:

693612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31930

American (AMR)

AF:

0.00

AC:

AN:

36552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25210

East Asian (EAS)

AF:

0.00

AC:

AN:

36362

South Asian (SAS)

AF:

0.0000125

AC:

AN:

79842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5242

European-Non Finnish (NFE)

AF:

0.00000739

AC:

AN:

1082258

Other (OTH)

AF:

0.0000172

AC:

AN:

58148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.044

M_CAP

Benign

0.042

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.90

PhyloP100

1.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.73

REVEL

Benign

0.15

Sift

Benign

0.19

Sift4G

Benign

0.10

Polyphen

0.22

Vest4

0.17

MutPred

0.14

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.55

MPC

0.50

ClinPred

0.23

GERP RS

4.3

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.11

gMVP

0.22

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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