Variant 7-151355774-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001243351.2(NUB1):c.422C>T(p.Thr141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 1,437,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

NUB1
NM_001243351.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

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:

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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=0.14760247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUB1	NM_001243351.2 linkuse as main transcript	c.422C>T	p.Thr141Ile	missense_variant	6/15	ENST00000568733.6	NP_001230280.2	Q9Y5A7-1H3BM74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUB1	ENST00000568733.6 linkuse as main transcript	c.422C>T	p.Thr141Ile	missense_variant	6/15	1	NM_001243351.2	ENSP00000454264.2		Q9Y5A7-1H3BM74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000466

AC:

AN:

214696

Hom.:

AF XY:

0.00000865

AC XY:

AN XY:

115606

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000556

AC:

AN:

1437666

Hom.:

Cov.:

AF XY:

0.00000701

AC XY:

AN XY:

712774

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:

0.00000727

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.00000378

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 submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.494C>T (p.T165I) alteration is located in exon 6 (coding exon 6) of the NUB1 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the threonine (T) at amino acid position 165 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

.;.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Benign

0.058

Sift

Benign

0.030

D;D;T;T

Sift4G

Benign

0.071

T;T;D;D

Polyphen

0.52

.;.;P;.

Vest4

0.32

MVP

0.43

MPC

0.50

ClinPred

0.50

GERP RS

3.0

Varity_R

0.094

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over