17-5386234-T-C

Position:

chr17-5386234-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002532.6(NUP88):c.2198A>G(p.Asn733Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00779 in 1,613,434 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 64 hom. )

Consequence

NUP88
NM_002532.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.88

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]

NUP88 links:

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RABEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069188774).

BP6

Variant 17-5386234-T-C is Benign according to our data. Variant chr17-5386234-T-C is described in ClinVar as [Benign]. Clinvar id is 2647295.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP88	NM_002532.6 linkuse as main transcript	c.2198A>G	p.Asn733Ser	missense_variant	17/17	ENST00000573584.6
RABEP1	NM_004703.6 linkuse as main transcript	c.*3011T>C		3_prime_UTR_variant	18/18	ENST00000537505.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP88	ENST00000573584.6 linkuse as main transcript	c.2198A>G	p.Asn733Ser	missense_variant	17/17	1	NM_002532.6	P1
RABEP1	ENST00000537505.6 linkuse as main transcript	c.*3011T>C		3_prime_UTR_variant	18/18	1	NM_004703.6	P1	Q15276-1

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

904

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00806

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00925

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00646

AC:

1620

AN:

250726

Hom.:

AF XY:

0.00676

AC XY:

916

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.00800

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00798

AC:

11666

AN:

1461120

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

5706

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00460

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00897

Gnomad4 NFE exome

AF:

0.00939

Gnomad4 OTH exome

AF:

0.00689

GnomAD4 genome

AF:

0.00594

AC:

904

AN:

152314

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

433

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.00925

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00815

Hom.:

Bravo

AF:

0.00597

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00703

AC:

853

EpiCase

AF:

0.00922

EpiControl

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NUP88-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

NUP88: BS1, BS2; RABEP1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

Sift4G

Uncertain

0.056

Polyphen

0.31

Vest4

0.34

MVP

0.52

MPC

0.41

ClinPred

0.027

GERP RS

3.9

Varity_R

0.16

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over