rs2287363

Positions:

Variant summary

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

The NM_015354.3(NUP188):c.4596A>C(p.Ser1532=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,612,342 control chromosomes in the GnomAD database, including 149,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14717 hom., cov: 32)

Exomes 𝑓: 0.43 ( 134613 hom. )

Consequence

NUP188
NM_015354.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.539

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:

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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=-0.61).

BP6

Variant 9-129005389-A-C is Benign according to our data. Variant chr9-129005389-A-C is described in ClinVar as [Benign]. Clinvar id is 403266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.539 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP188	NM_015354.3 linkuse as main transcript	c.4596A>C	p.Ser1532=	synonymous_variant	40/44	ENST00000372577.2	NP_056169.1
LOC101929314	XR_007061810.1 linkuse as main transcript	n.85-92T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP188	ENST00000372577.2 linkuse as main transcript	c.4596A>C	p.Ser1532=	synonymous_variant	40/44	1	NM_015354.3	ENSP00000361658	P1	Q5SRE5-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66560

AN:

151884

Hom.:

14686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.435

AC:

108657

AN:

249614

Hom.:

23996

AF XY:

0.430

AC XY:

58104

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.458

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.428

AC:

624941

AN:

1460342

Hom.:

134613

Cov.:

AF XY:

0.426

AC XY:

309655

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.359

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.438

AC:

66647

AN:

152000

Hom.:

14717

Cov.:

AF XY:

0.440

AC XY:

32684

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.457

Gnomad4 AMR

AF:

0.484

Gnomad4 ASJ

AF:

0.397

Gnomad4 EAS

AF:

0.392

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.427

Hom.:

33190

Bravo

AF:

0.442

Asia WGS

AF:

0.387

AC:

1351

AN:

3478

EpiCase

AF:

0.421

EpiControl

AF:

0.418

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, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.61

CADD

Benign

9.8

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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