9-128999620-A-G

Variant names:

Variant summary

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

The NM_015354.3(NUP188):c.3662-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,611,356 control chromosomes in the GnomAD database, including 117,674 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8591 hom., cov: 31)

Exomes 𝑓: 0.38 ( 109083 hom. )

Consequence

NUP188
NM_015354.3 splice_region, intron

Scores

Splicing: ADA: 0.00005606

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.120

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=-0.85).

BP6

Variant 9-128999620-A-G is Benign according to our data. Variant chr9-128999620-A-G is described in ClinVar as [Benign]. Clinvar id is 403264.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.3662-4A>G		splice_region_variant, intron_variant	Intron 33 of 43	ENST00000372577.2	NP_056169.1	Q5SRE5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUP188	ENST00000372577.2 link	c.3662-4A>G	splice_region_variant, intron_variant	Intron 33 of 43	1	NM_015354.3	ENSP00000361658.2	Q5SRE5-1
NUP188	ENST00000477069.5 link	n.1630-4A>G	splice_region_variant, intron_variant	Intron 14 of 18	1
NUP188	ENST00000487952.1 link	n.20A>G	non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47285

AN:

151808

Hom.:

8581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.361

AC:

90411

AN:

250458

Hom.:

17377

AF XY:

0.364

AC XY:

49252

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.347

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.381

AC:

556662

AN:

1459430

Hom.:

109083

Cov.:

AF XY:

0.381

AC XY:

276595

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.311

AC:

47302

AN:

151926

Hom.:

8591

Cov.:

AF XY:

0.313

AC XY:

23273

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.376

Hom.:

14220

Bravo

AF:

0.303

Asia WGS

AF:

0.252

AC:

880

AN:

3478

EpiCase

AF:

0.396

EpiControl

AF:

0.394

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 -

NUP188-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

-0.85

CADD

Benign

5.1

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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