6-17616656-T-C

Variant summary

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

The NM_005124.4(NUP153):ā€‹c.4214A>Gā€‹(p.Asn1405Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,806 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15107623).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP153NM_005124.4 linkc.4214A>G p.Asn1405Ser missense_variant 21/22 ENST00000262077.3 NP_005115.2 P49790-1
NUP153NM_001278209.2 linkc.4307A>G p.Asn1436Ser missense_variant 22/23 NP_001265138.1 P49790-3
NUP153NM_001278210.2 linkc.4088A>G p.Asn1363Ser missense_variant 20/21 NP_001265139.1 P49790-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP153ENST00000262077.3 linkc.4214A>G p.Asn1405Ser missense_variant 21/221 NM_005124.4 ENSP00000262077.3 P49790-1
NUP153ENST00000613258.4 linkc.4088A>G p.Asn1363Ser missense_variant 20/211 ENSP00000478627.1 P49790-2
NUP153ENST00000537253.5 linkc.4307A>G p.Asn1436Ser missense_variant 22/232 ENSP00000444029.1 P49790-3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251180
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135762
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461606
Hom.:
0
Cov.:
31
AF XY:
0.0000248
AC XY:
18
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsFeb 22, 2023The c.4214A>G (p.N1405S) alteration is located in exon 21 (coding exon 21) of the NUP153 gene. This alteration results from a A to G substitution at nucleotide position 4214, causing the asparagine (N) at amino acid position 1405 to be replaced by a serine (S). 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
0.064
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.059
.;.;T
Eigen
Benign
0.066
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
.;.;M
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.0
.;D;D
REVEL
Benign
0.16
Sift
Benign
0.085
.;T;T
Sift4G
Benign
0.86
T;T;T
Polyphen
0.36
.;.;B
Vest4
0.18
MutPred
0.13
.;.;Loss of stability (P = 0.1164);
MVP
0.61
MPC
0.045
ClinPred
0.15
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.19

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.

Other links and lift over

dbSNP: rs773777225; hg19: chr6-17616887; API