rs12336276

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015354.3(NUP188):c.4044+6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,612,086 control chromosomes in the GnomAD database, including 14,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron

Scores

Splicing: ADA: 0.0003852

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUP188	NM_015354.3 link	c.4044+6A>C		splice_region_variant, intron_variant	Intron 35 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.4044+6A>C	splice_region_variant, intron_variant	Intron 35 of 43	1	NM_015354.3	ENSP00000361658.2	Q5SRE5-1
NUP188	ENST00000477069.5 link	n.2012+6A>C	splice_region_variant, intron_variant	Intron 16 of 18	1
NUP188	ENST00000487952.1 link	n.412A>C	non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.142

AC:

35111

AN:

247670

AF XY:

0.141

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 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

AC:

11423

AN:

33446

Gnomad4 AMR exome

AF:

0.110

AC:

4882

AN:

44484

Gnomad4 ASJ exome

AF:

0.0943

AC:

2460

AN:

26086

Gnomad4 EAS exome

AF:

0.312

AC:

12353

AN:

39628

Gnomad4 SAS exome

AF:

0.220

AC:

18950

AN:

86054

Gnomad4 FIN exome

AF:

0.107

AC:

5665

AN:

52932

Gnomad4 NFE exome

AF:

0.0860

AC:

95624

AN:

1111278

Gnomad4 Remaining exome

AF:

0.127

AC:

7663

AN:

60352

Heterozygous variant carriers

7867

15734

23602

31469

39336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

3928

7856

11784

15712

19640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.33736

AN:

0.33736

Gnomad4 AMR

AF:

0.118

AC:

0.118213

AN:

0.118213

Gnomad4 ASJ

AF:

0.0888

AC:

0.088812

AN:

0.088812

Gnomad4 EAS

AF:

0.309

AC:

0.308829

AN:

0.308829

Gnomad4 SAS

AF:

0.238

AC:

0.237562

AN:

0.237562

Gnomad4 FIN

AF:

0.118

AC:

0.117597

AN:

0.117597

Gnomad4 NFE

AF:

0.0872

AC:

0.0872488

AN:

0.0872488

Gnomad4 OTH

AF:

0.145

AC:

0.14455

AN:

0.14455

Heterozygous variant carriers

1006

2012

3018

4024

5030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.161

Hom.:

1888

Bravo

AF:

0.178

Asia WGS

AF:

0.265

AC:

921

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 25, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Nov 14, 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). -

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

-0.73

CADD

Benign

8.6

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

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