6-17624770-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005124.4(NUP153):ā€‹c.3965A>Gā€‹(p.Asn1322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.324
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042847365).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP153NM_005124.4 linkc.3965A>G p.Asn1322Ser missense_variant 20/22 ENST00000262077.3 NP_005115.2 P49790-1
NUP153NM_001278209.2 linkc.4058A>G p.Asn1353Ser missense_variant 21/23 NP_001265138.1 P49790-3
NUP153NM_001278210.2 linkc.3839A>G p.Asn1280Ser missense_variant 19/21 NP_001265139.1 P49790-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP153ENST00000262077.3 linkc.3965A>G p.Asn1322Ser missense_variant 20/221 NM_005124.4 ENSP00000262077.3 P49790-1
NUP153ENST00000613258.4 linkc.3839A>G p.Asn1280Ser missense_variant 19/211 ENSP00000478627.1 P49790-2
NUP153ENST00000537253.5 linkc.4058A>G p.Asn1353Ser missense_variant 21/232 ENSP00000444029.1 P49790-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsMar 13, 2023The c.3965A>G (p.N1322S) alteration is located in exon 20 (coding exon 20) of the NUP153 gene. This alteration results from a A to G substitution at nucleotide position 3965, causing the asparagine (N) at amino acid position 1322 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
0.052
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
7.6
DANN
Benign
0.93
DEOGEN2
Benign
0.0062
.;.;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.51
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.043
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.045
.;.;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.5
.;N;N
REVEL
Benign
0.055
Sift
Benign
0.40
.;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.14
MutPred
0.13
.;.;Gain of glycosylation at N1322 (P = 0.0074);
MVP
0.27
MPC
0.028
ClinPred
0.064
T
GERP RS
-3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.026
gMVP
0.11

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: rs750780211; hg19: chr6-17625001; API