7-151376796-C-A

Variant names:

Variant summary

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

The NM_001243351.2(NUB1):c.1654C>A(p.Pro552Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,433,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P552S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

NUB1
NM_001243351.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

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]

NUB1 links:

WDR86 (HGNC:28020): (WD repeat domain 86)

WDR86 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=0.13101447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUB1	NM_001243351.2	MANE Select	c.1654C>A	p.Pro552Thr	missense	Exon 14 of 15	NP_001230280.2	Q9Y5A7-1
NUB1	NM_001363529.2		c.1654C>A	p.Pro552Thr	missense	Exon 14 of 15	NP_001350458.1	Q9Y5A7-1
NUB1	NM_001385353.1		c.1612C>A	p.Pro538Thr	missense	Exon 14 of 15	NP_001372282.1	Q9Y5A7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUB1	ENST00000568733.6	TSL:1 MANE Select	c.1654C>A	p.Pro552Thr	missense	Exon 14 of 15	ENSP00000454264.2	Q9Y5A7-1
NUB1	ENST00000413040.7	TSL:1	c.1612C>A	p.Pro538Thr	missense	Exon 14 of 15	ENSP00000398644.3	Q9Y5A7-2
NUB1	ENST00000866417.1		c.1708C>A	p.Pro570Thr	missense	Exon 15 of 16	ENSP00000536476.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000419

AC:

AN:

1433092

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32984

American (AMR)

AF:

0.00

AC:

AN:

39584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

38336

South Asian (SAS)

AF:

0.00

AC:

AN:

82136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000546

AC:

AN:

1098774

Other (OTH)

AF:

0.00

AC:

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.0098

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

2.4

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.44

REVEL

Benign

0.090

Sift

Benign

0.26

Sift4G

Uncertain

0.030

Polyphen

0.0050

Vest4

0.35

MutPred

0.13

Gain of phosphorylation at P552 (P = 0.0076)

MVP

0.47

MPC

0.42

ClinPred

0.32

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.29

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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