rs2004632

Variant names:

• chr9-128999158-A-G
• rs2004632
• NM_015354.3:c.3516-14A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-128999158-A-G
• chr9-128999158-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.55
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• sandestig-stefanova syndrome

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC101929314 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.3516-14A>G		intron_variant	Intron 32 of 43	ENST00000372577.2	NP_056169.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46827 AN: 151926 Hom.: 8483 Cov.: 32

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

GnomAD2 exomes AF: 0.355 AC: 89012 AN: 250688 AF XY: 0.357

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 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.: 32 AF XY: 0.377 AC XY: 273610 AN XY: 725924

African (AFR) AF: 0.112 AC: 3742 AN: 33440

American (AMR) AF: 0.429 AC: 19157 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8919 AN: 26070

East Asian (EAS) AF: 0.135 AC: 5340 AN: 39668

South Asian (SAS) AF: 0.317 AC: 27360 AN: 86188

European-Finnish (FIN) AF: 0.393 AC: 20930 AN: 53232

Middle Eastern (MID) AF: 0.398 AC: 2276 AN: 5724

European-Non Finnish (NFE) AF: 0.399 AC: 442638 AN: 1109942

Other (OTH) AF: 0.355 AC: 21407 AN: 60282

GnomAD4 genome AF: 0.308 AC: 46851 AN: 152044 Hom.: 8493 Cov.: 32 AF XY: 0.310 AC XY: 23026 AN XY: 74324

African (AFR) AF: 0.119 AC: 4958 AN: 41508

American (AMR) AF: 0.393 AC: 6009 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3470

East Asian (EAS) AF: 0.174 AC: 897 AN: 5166

South Asian (SAS) AF: 0.304 AC: 1465 AN: 4818

European-Finnish (FIN) AF: 0.405 AC: 4274 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26902 AN: 67930

Other (OTH) AF: 0.336 AC: 708 AN: 2110

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

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2004632; hg19: chr9-131761437; COSMIC: COSV65361744; COSMIC: COSV65361744;