rs1555448026

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174916.3(UBR1):ā€‹c.1370A>Gā€‹(p.Asn457Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

UBR1
NM_174916.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88
Variant links:
Genes affected
UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

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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=0.13726851).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UBR1NM_174916.3 linkc.1370A>G p.Asn457Ser missense_variant 12/47 ENST00000290650.9 NP_777576.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UBR1ENST00000290650.9 linkc.1370A>G p.Asn457Ser missense_variant 12/471 NM_174916.3 ENSP00000290650.4 Q8IWV7-1
UBR1ENST00000546274.6 linkc.1370A>G p.Asn457Ser missense_variant 12/292 ENSP00000477932.1 A0A087WTJ9
UBR1ENST00000563239.1 linkn.*203-7522A>G intron_variant 3 ENSP00000456502.1 H3BS20
UBR1ENST00000569971.5 linkn.*91+1533A>G intron_variant 4 ENSP00000455759.1 H3BQF8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461826
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727218
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoApr 08, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
-0.083
Eigen_PC
Benign
0.059
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.13
Sift
Uncertain
0.020
D;.
Sift4G
Benign
0.15
T;T
Polyphen
0.28
B;.
Vest4
0.15
MutPred
0.39
Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
0.61
MPC
0.46
ClinPred
0.69
D
GERP RS
3.3
Varity_R
0.10
gMVP
0.088

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: rs1555448026; hg19: chr15-43347009; API