Variant 6-17625876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005124.4(NUP153):c.3833G>A(p.Gly1278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

Variant links:

Genes affected

NUP153 (HGNC:8062): (nucleoporin 153) Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

NUP153 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23940289).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP153	NM_005124.4 linkuse as main transcript	c.3833G>A	p.Gly1278Glu	missense_variant	19/22	ENST00000262077.3	NP_005115.2	P49790-1
NUP153	NM_001278209.2 linkuse as main transcript	c.3926G>A	p.Gly1309Glu	missense_variant	20/23		NP_001265138.1	P49790-3
NUP153	NM_001278210.2 linkuse as main transcript	c.3707G>A	p.Gly1236Glu	missense_variant	18/21		NP_001265139.1	P49790-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUP153	ENST00000262077.3 linkuse as main transcript	c.3833G>A	p.Gly1278Glu	missense_variant	19/22	1	NM_005124.4	ENSP00000262077.3	P49790-1
NUP153	ENST00000613258.4 linkuse as main transcript	c.3707G>A	p.Gly1236Glu	missense_variant	18/21	1		ENSP00000478627.1	P49790-2
NUP153	ENST00000537253.5 linkuse as main transcript	c.3926G>A	p.Gly1309Glu	missense_variant	20/23	2		ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251270

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135782

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

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:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Aug 12, 2021

The c.3833G>A (p.G1278E) alteration is located in exon 19 (coding exon 19) of the NUP153 gene. This alteration results from a G to A substitution at nucleotide position 3833, causing the glycine (G) at amino acid position 1278 to be replaced by a glutamic acid (E). 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

0.22

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

.;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.2

.;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.014

.;D;D

Sift4G

Benign

0.17

T;T;T

Polyphen

0.79

.;.;P

Vest4

0.47

MutPred

0.21

.;.;Loss of catalytic residue at A1279 (P = 0.1104);

MVP

0.28

MPC

0.14

ClinPred

0.69

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.48

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