chr14-93210703-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_175748.4(UBR7):​c.340C>T​(p.Leu114Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,608,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

UBR7
NM_175748.4 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027472317).
BP6
Variant 14-93210703-C-T is Benign according to our data. Variant chr14-93210703-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3813127.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000118 (18/152288) while in subpopulation AFR AF= 0.000433 (18/41560). AF 95% confidence interval is 0.000279. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBR7NM_175748.4 linkc.340C>T p.Leu114Phe missense_variant Exon 3 of 11 ENST00000013070.11 NP_786924.2
UBR7NR_038150.2 linkn.242C>T non_coding_transcript_exon_variant Exon 2 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBR7ENST00000013070.11 linkc.340C>T p.Leu114Phe missense_variant Exon 3 of 11 1 NM_175748.4 ENSP00000013070.6 Q8N806
ENSG00000259066ENST00000557574.1 linkc.397C>T p.Leu133Phe missense_variant Exon 4 of 5 4 ENSP00000451369.1 G3V3Q6

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000246
AC:
6
AN:
243682
Hom.:
0
AF XY:
0.00000760
AC XY:
1
AN XY:
131622
show subpopulations
Gnomad AFR exome
AF:
0.000381
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1456092
Hom.:
0
Cov.:
30
AF XY:
0.0000111
AC XY:
8
AN XY:
723958
show subpopulations
Gnomad4 AFR exome
AF:
0.000449
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000177
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152288
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000433
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000257
Hom.:
0
Bravo
AF:
0.000185
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 01, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.034
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
16
DANN
Benign
0.78
DEOGEN2
Benign
0.0041
.;T;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.39
N
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.027
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
.;N;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.84
N;N;N
REVEL
Benign
0.098
Sift
Benign
0.72
T;T;T
Sift4G
Benign
0.71
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.16
MVP
0.51
MPC
0.50
ClinPred
0.057
T
GERP RS
3.6
Varity_R
0.031
gMVP
0.44

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.

Other links and lift over

dbSNP: rs535218313; hg19: chr14-93677049; COSMIC: COSV50151080; COSMIC: COSV50151080; API