rs1798292031

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001243351.2(NUB1):​c.1568C>G​(p.Ala523Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A523V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

NUB1
NM_001243351.2 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.98

Publications

0 publications found
Variant links:
Genes affected
NUB1 (HGNC:17623): (negative regulator of ubiquitin like proteins 1) This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]
WDR86 (HGNC:28020): (WD repeat domain 86)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38966638).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUB1NM_001243351.2 linkc.1568C>G p.Ala523Gly missense_variant Exon 14 of 15 ENST00000568733.6 NP_001230280.2 Q9Y5A7-1H3BM74

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUB1ENST00000568733.6 linkc.1568C>G p.Ala523Gly missense_variant Exon 14 of 15 1 NM_001243351.2 ENSP00000454264.2 Q9Y5A7-1H3BM74

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.036
T;T;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.39
T;T;T
MetaSVM
Uncertain
0.023
D
MutationAssessor
Uncertain
2.5
.;.;M
PhyloP100
6.0
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.4
N;N;.
REVEL
Uncertain
0.30
Sift
Uncertain
0.010
D;D;.
Sift4G
Uncertain
0.024
D;D;.
Polyphen
0.97
.;.;D
Vest4
0.60
MutPred
0.63
.;.;Loss of stability (P = 0.0639);
MVP
0.43
MPC
0.36
ClinPred
0.92
D
GERP RS
5.6
Varity_R
0.22
gMVP
0.56
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs1798292031; hg19: chr7-151073796; API