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GeneBe

17-5386713-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002532.6(NUP88):c.2157A>G(p.Lys719=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,594,484 control chromosomes in the GnomAD database, including 153,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 15298 hom., cov: 32)
Exomes 𝑓: 0.43 ( 138001 hom. )

Consequence

NUP88
NM_002532.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0130
Variant links:
Genes affected
NUP88 (HGNC:8067): (nucleoporin 88) 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, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-5386713-T-C is Benign according to our data. Variant chr17-5386713-T-C is described in ClinVar as [Benign]. Clinvar id is 1327043.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.013 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUP88NM_002532.6 linkuse as main transcriptc.2157A>G p.Lys719= synonymous_variant 16/17 ENST00000573584.6
NUP88NM_001320653.2 linkuse as main transcriptc.2205A>G p.Lys735= synonymous_variant 16/17
NUP88XM_047436155.1 linkuse as main transcriptc.1812A>G p.Lys604= synonymous_variant 16/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUP88ENST00000573584.6 linkuse as main transcriptc.2157A>G p.Lys719= synonymous_variant 16/171 NM_002532.6 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.437
AC:
66423
AN:
151992
Hom.:
15289
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.415
Gnomad AMI
AF:
0.213
Gnomad AMR
AF:
0.413
Gnomad ASJ
AF:
0.388
Gnomad EAS
AF:
0.837
Gnomad SAS
AF:
0.649
Gnomad FIN
AF:
0.588
Gnomad MID
AF:
0.453
Gnomad NFE
AF:
0.392
Gnomad OTH
AF:
0.428
GnomAD3 exomes
AF:
0.477
AC:
119820
AN:
251288
Hom.:
30982
AF XY:
0.481
AC XY:
65335
AN XY:
135814
show subpopulations
Gnomad AFR exome
AF:
0.414
Gnomad AMR exome
AF:
0.431
Gnomad ASJ exome
AF:
0.392
Gnomad EAS exome
AF:
0.839
Gnomad SAS exome
AF:
0.634
Gnomad FIN exome
AF:
0.579
Gnomad NFE exome
AF:
0.388
Gnomad OTH exome
AF:
0.457
GnomAD4 exome
AF:
0.425
AC:
613504
AN:
1442374
Hom.:
138001
Cov.:
29
AF XY:
0.431
AC XY:
310067
AN XY:
718948
show subpopulations
Gnomad4 AFR exome
AF:
0.405
Gnomad4 AMR exome
AF:
0.429
Gnomad4 ASJ exome
AF:
0.382
Gnomad4 EAS exome
AF:
0.842
Gnomad4 SAS exome
AF:
0.622
Gnomad4 FIN exome
AF:
0.557
Gnomad4 NFE exome
AF:
0.388
Gnomad4 OTH exome
AF:
0.451
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.437
AC:
66476
AN:
152110
Hom.:
15298
Cov.:
32
AF XY:
0.452
AC XY:
33638
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.415
Gnomad4 AMR
AF:
0.413
Gnomad4 ASJ
AF:
0.388
Gnomad4 EAS
AF:
0.837
Gnomad4 SAS
AF:
0.648
Gnomad4 FIN
AF:
0.588
Gnomad4 NFE
AF:
0.392
Gnomad4 OTH
AF:
0.433
Alfa
AF:
0.397
Hom.:
6104
Bravo
AF:
0.421
Asia WGS
AF:
0.749
AC:
2600
AN:
3478
EpiCase
AF:
0.396
EpiControl
AF:
0.395

ClinVar

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

Submissions by phenotype

Fetal akinesia deformation sequence 4 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
8.4
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1071705; hg19: chr17-5290033; COSMIC: COSV52582787; COSMIC: COSV52582787; API