14-93207314-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A8D) 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

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22
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]
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]

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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=0.13661638).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBR7NM_175748.4 linkc.23C>T p.Ala8Val missense_variant Exon 1 of 11 ENST00000013070.11 NP_786924.2
UBR7NR_038150.2 linkn.59C>T non_coding_transcript_exon_variant Exon 1 of 10
GON7NM_032490.5 linkc.-277G>A upstream_gene_variant ENST00000306954.5 NP_115879.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBR7ENST00000013070.11 linkc.23C>T p.Ala8Val missense_variant Exon 1 of 11 1 NM_175748.4 ENSP00000013070.6 Q8N806
ENSG00000259066ENST00000557574.1 linkc.208-2510C>T intron_variant Intron 2 of 4 4 ENSP00000451369.1 G3V3Q6
GON7ENST00000306954.5 linkc.-277G>A upstream_gene_variant 1 NM_032490.5 ENSP00000306320.4 Q9BXV9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000712
AC:
10
AN:
1405144
Hom.:
0
Cov.:
33
AF XY:
0.00000865
AC XY:
6
AN XY:
693612
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:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000739
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0096
T;T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.044
N
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.90
L;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.73
N;N;N
REVEL
Benign
0.15
Sift
Benign
0.19
T;T;D
Sift4G
Benign
0.10
T;T;T
Polyphen
0.22
B;.;.
Vest4
0.17
MutPred
0.14
Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);
MVP
0.55
MPC
0.50
ClinPred
0.23
T
GERP RS
4.3
Varity_R
0.11
gMVP
0.22

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

LitVar

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

Other links and lift over

dbSNP: rs149784475; hg19: chr14-93673659; API