rs2004632

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015354.3(NUP188):c.3516-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,611,260 control chromosomes in the GnomAD database, including 116,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8493 hom., cov: 32)

Exomes 𝑓: 0.38 ( 107886 hom. )

Consequence

NUP188
NM_015354.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.55

Variant links:

Genes affected

NUP188 (HGNC:17859): (nucleoporin 188) The nuclear pore complex (NPC) is found on the nuclear envelope and forms a gateway that regulates the flow of proteins and RNAs between the cytoplasm and nucleoplasm. The NPC is comprised of approximately 30 distinct proteins collectively known as nucleoporins. Nucleoporins are pore-complex-specific glycoproteins which often have cytoplasmically oriented O-linked N-acetylglucosamine residues and numerous repeats of the pentapeptide sequence XFXFG. However, the nucleoporin protein encoded by this gene does not contain the typical FG repeat sequences found in most vertebrate nucleoporins. This nucleoporin is thought to form part of the scaffold for the central channel of the nuclear pore. [provided by RefSeq, Jan 2013]

NUP188 links:

LOC101929314 (HGNC:):

LOC101929314 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-128999158-A-G is Benign according to our data. Variant chr9-128999158-A-G is described in ClinVar as [Benign]. Clinvar id is 403263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP188	NM_015354.3 link	c.3516-14A>G		intron_variant	Intron 32 of 43	ENST00000372577.2	NP_056169.1	Q5SRE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP188	ENST00000372577.2 link	c.3516-14A>G		intron_variant	Intron 32 of 43	1	NM_015354.3	ENSP00000361658.2		Q5SRE5-1
NUP188	ENST00000477069.5 link	n.1484-14A>G		intron_variant	Intron 13 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46827

AN:

151926

Hom.:

8483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.355

AC:

89012

AN:

250688

Hom.:

17021

AF XY:

0.357

AC XY:

48368

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.172

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.378

AC:

551769

AN:

1459216

Hom.:

107886

Cov.:

AF XY:

0.377

AC XY:

273610

AN XY:

725924

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.308

AC:

46851

AN:

152044

Hom.:

8493

Cov.:

AF XY:

0.310

AC XY:

23026

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.354

Hom.:

2291

Bravo

AF:

0.301

Asia WGS

AF:

0.224

AC:

781

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sandestig-stefanova syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.70

DANN

Benign

0.58

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