Variant chr17-5386260-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002532.6(NUP88):c.2172T>C(p.His724=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,607,144 control chromosomes in the GnomAD database, including 148,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16313 hom., cov: 32)

Exomes 𝑓: 0.41 ( 132095 hom. )

Consequence

NUP88
NM_002532.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.54

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-5386260-A-G is Benign according to our data. Variant chr17-5386260-A-G is described in ClinVar as [Benign]. Clinvar id is 1327042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.55 with no splicing effect.

BA1

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	Protein	UniProt
NUP88	NM_002532.6 linkuse as main transcript	c.2172T>C	p.His724=	synonymous_variant	17/17	ENST00000573584.6	NP_002523.2
RABEP1	NM_004703.6 linkuse as main transcript	c.*3037A>G		3_prime_UTR_variant	18/18	ENST00000537505.6	NP_004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP88	ENST00000573584.6 linkuse as main transcript	c.2172T>C	p.His724=	synonymous_variant	17/17	1	NM_002532.6	ENSP00000458954	P1
RABEP1	ENST00000537505.6 linkuse as main transcript	c.*3037A>G		3_prime_UTR_variant	18/18	1	NM_004703.6	ENSP00000445408	P1	Q15276-1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68536

AN:

151782

Hom.:

16290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.837

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.432

GnomAD3 exomes

AF:

0.470

AC:

116930

AN:

248898

Hom.:

30009

AF XY:

0.471

AC XY:

63390

AN XY:

134508

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.839

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.444

GnomAD4 exome

AF:

0.413

AC:

600816

AN:

1455244

Hom.:

132095

Cov.:

AF XY:

0.418

AC XY:

302980

AN XY:

724014

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.842

Gnomad4 SAS exome

AF:

0.617

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.452

AC:

68612

AN:

151900

Hom.:

16313

Cov.:

AF XY:

0.465

AC XY:

34543

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.837

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.397

Hom.:

8919

Bravo

AF:

0.441

Asia WGS

AF:

0.751

AC:

2604

AN:

3476

EpiCase

AF:

0.374

EpiControl

AF:

0.374

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Fetal akinesia deformation sequence 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.4

DANN

Benign

0.89

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