rs2004632

chr9-128999158-A-Gchr9-128999158-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015354.3(NUP188):c.3516-14A>G variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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]

LOC101929314 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
NUP188	NM_015354.3	c.3516-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000372577.2
LOC101929314	XR_007061810.1	n.163-5124T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP188	ENST00000372577.2	c.3516-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015354.3	P1
NUP188	ENST00000477069.5	n.1484-14A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.355 AC: 89012 AN: 250688 Hom.: 17021 AF XY: 0.357 AC XY: 48368 AN XY: 135500

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 SAS exome AF: 0.318

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

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.355

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.336

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:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

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	-0.82
Cadd	Benign	0.70
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

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