NM_001243351.2:c.12G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001243351.2(NUB1):c.12G>T(p.Lys4Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0112 in 1,609,544 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 136 hom. )

Consequence

NUB1
NM_001243351.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.60

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006970763).

BP6

Variant 7-151345361-G-T is Benign according to our data. Variant chr7-151345361-G-T is described in ClinVar as [Benign]. Clinvar id is 774318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUB1	NM_001243351.2 link	c.12G>T	p.Lys4Asn	missense_variant	Exon 2 of 15	ENST00000568733.6	NP_001230280.2	Q9Y5A7-1H3BM74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUB1	ENST00000568733.6 link	c.12G>T	p.Lys4Asn	missense_variant	Exon 2 of 15	1	NM_001243351.2	ENSP00000454264.2		Q9Y5A7-1H3BM74

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00805

AC:

1994

AN:

247654

AF XY:

0.00801

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00964

GnomAD4 exome

AF:

0.0116

AC:

16906

AN:

1457312

Hom.:

136

Cov.:

AF XY:

0.0112

AC XY:

8156

AN XY:

725194

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33358

American (AMR)

AF:

0.00401

AC:

178

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.00346

AC:

297

AN:

85938

European-Finnish (FIN)

AF:

0.0153

AC:

814

AN:

53348

Middle Eastern (MID)

AF:

0.00522

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0136

AC:

15027

AN:

1108694

Other (OTH)

AF:

0.00845

AC:

509

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

678

1356

2033

2711

3389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00756

AC:

1151

AN:

152232

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

572

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41558

American (AMR)

AF:

0.00549

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00332

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0170

AC:

180

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

762

AN:

68008

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00640

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00749

AC:

905

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0115

EpiControl

AF:

0.00951

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

T;T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

.;.;L;.

PhyloP100

3.6

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.21

N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Benign

0.29

T;T;D;D

Polyphen

0.94

.;.;P;.

Vest4

0.54

MutPred

0.24

.;.;Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);

MVP

0.50

MPC

0.50

ClinPred

0.019

GERP RS

5.6

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.18

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001243351.2:c.12G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over