Genetic Variant NUP188:c.32+137G>A (chr9-128947888-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_015354.3(NUP188):c.32+137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 801,760 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 29 hom. )

Consequence

NUP188
NM_015354.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.485

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:

ENSG00000251184 (HGNC:):

ENSG00000251184 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-128947888-G-A is Benign according to our data. Variant chr9-128947888-G-A is described in ClinVar as [Benign]. Clinvar id is 1264437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP188	NM_015354.3 link	c.32+137G>A		intron_variant	Intron 1 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.32+137G>A	intron_variant	Intron 1 of 43	1	NM_015354.3	ENSP00000361658.2	Q5SRE5-1
ENSG00000251184	ENST00000482796.1 link	c.39-1301G>A	intron_variant	Intron 1 of 4	2		ENSP00000417556.2	H7C4K7
NUP188	ENST00000491990.5 link	n.45+137G>A	intron_variant	Intron 1 of 5	5
NUP188	ENST00000550219.1 link	n.-129G>A	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2429

AN:

151590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00913

GnomAD4 exome

AF:

0.00161

AC:

1047

AN:

650054

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

459

AN XY:

318080

show subpopulations

Gnomad4 AFR exome

AF:

0.0569

Gnomad4 AMR exome

AF:

0.00439

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00443

GnomAD4 genome

AF:

0.0161

AC:

2437

AN:

151706

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1096

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.0564

Gnomad4 AMR

AF:

0.00485

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00904

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jul 09, 2018

GeneDx

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

-0.81

CADD

Benign

9.2

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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