chr16-56748377-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014669.5(NUP93):​c.130C>T​(p.Arg44Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,826 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

NUP93
NM_014669.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97
Variant links:
Genes affected
NUP93 (HGNC:28958): (nucleoporin 93) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29654622).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP93NM_014669.5 linkuse as main transcriptc.130C>T p.Arg44Cys missense_variant 2/22 ENST00000308159.10 NP_055484.3
NUP93XM_005256263.4 linkuse as main transcriptc.130C>T p.Arg44Cys missense_variant 2/22 XP_005256320.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP93ENST00000308159.10 linkuse as main transcriptc.130C>T p.Arg44Cys missense_variant 2/221 NM_014669.5 ENSP00000310668 P1Q8N1F7-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250746
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135594
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461672
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000809
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000569
Hom.:
0
Bravo
AF:
0.0000189
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2022The c.130C>T (p.R44C) alteration is located in exon 2 (coding exon 1) of the NUP93 gene. This alteration results from a C to T substitution at nucleotide position 130, causing the arginine (R) at amino acid position 44 to be replaced by a cysteine (C). 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
0.28
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.063
T;T;T;T;T
Eigen
Benign
0.11
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.30
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.8
N;N;N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.029
D;D;T;T;D
Sift4G
Benign
0.065
T;T;D;T;T
Polyphen
0.97
D;.;.;.;.
Vest4
0.43
MutPred
0.41
Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);
MVP
0.71
MPC
0.45
ClinPred
0.71
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.26
gMVP
0.72

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: rs754633729; hg19: chr16-56782289; COSMIC: COSV57429982; API