Variant rs2274136 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005124.4(NUP153):c.2479G>T(p.Ala827Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 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. A827T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.287

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08268002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NUP153	NM_005124.4 linkuse as main transcript	c.2479G>T	p.Ala827Ser	missense_variant	17/22	ENST00000262077.3
NUP153	NM_001278209.2 linkuse as main transcript	c.2572G>T	p.Ala858Ser	missense_variant	18/23
NUP153	NM_001278210.2 linkuse as main transcript	c.2353G>T	p.Ala785Ser	missense_variant	16/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP153	ENST00000262077.3 linkuse as main transcript	c.2479G>T	p.Ala827Ser	missense_variant	17/22	1	NM_005124.4	P1	P49790-1
NUP153	ENST00000613258.4 linkuse as main transcript	c.2353G>T	p.Ala785Ser	missense_variant	16/21	1			P49790-2
NUP153	ENST00000537253.5 linkuse as main transcript	c.2572G>T	p.Ala858Ser	missense_variant	18/23	2			P49790-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145950

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1402862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698586

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

145950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70544

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0039

.;.;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.073

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

0.20

.;N;N

REVEL

Benign

0.020

Sift

Benign

0.31

.;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.0040

.;.;B

Vest4

0.15

MutPred

0.27

.;.;Gain of phosphorylation at A827 (P = 0.0055);

MVP

0.25

MPC

0.036

ClinPred

0.37

GERP RS

1.1

Varity_R

0.022

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over