rs12336276

Positions:

Variant summary

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

The NM_015354.3(NUP188):c.4044+6A>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,612,086 control chromosomes in the GnomAD database, including 14,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3237 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11693 hom. )

Consequence

NUP188
NM_015354.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0003852

Clinical Significance

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

Conservation

PhyloP100: 1.06

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=-0.73).

BP6

Variant 9-129001735-A-C is Benign according to our data. Variant chr9-129001735-A-C is described in ClinVar as [Benign]. Clinvar id is 403265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP188	NM_015354.3 linkuse as main transcript	c.4044+6A>C		splice_donor_region_variant, intron_variant		ENST00000372577.2
LOC101929314	XR_007061810.1 linkuse as main transcript	n.162+3485T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP188	ENST00000372577.2 linkuse as main transcript	c.4044+6A>C	splice_donor_region_variant, intron_variant		1	NM_015354.3	P1	Q5SRE5-1
NUP188	ENST00000477069.5 linkuse as main transcript	n.2012+6A>C	splice_donor_region_variant, intron_variant, non_coding_transcript_variant		1
NUP188	ENST00000487952.1 linkuse as main transcript	n.412A>C	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26379

AN:

151972

Hom.:

3233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0872

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.142

AC:

35111

AN:

247670

Hom.:

3377

AF XY:

0.141

AC XY:

18901

AN XY:

134116

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0964

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0851

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.109

AC:

159741

AN:

1459996

Hom.:

11693

Cov.:

AF XY:

0.112

AC XY:

81171

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.342

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.0943

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0860

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.174

AC:

26408

AN:

152090

Hom.:

3237

Cov.:

AF XY:

0.177

AC XY:

13127

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.0872

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.123

Hom.:

701

Bravo

AF:

0.178

Asia WGS

AF:

0.265

AC:

921

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 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

GeneDx

Feb 25, 2020

- -

Sandestig-stefanova syndrome

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

-0.73

CADD

Benign

8.6

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.010

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