Variant chr16-56758448-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014669.5(NUP93):c.180-90C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 938,472 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 33 hom., cov: 32)

Exomes 𝑓: 0.010 ( 108 hom. )

Consequence

NUP93
NM_014669.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.162

Variant links:

Genes affected

NUP93 (HGNC:28958): (nucleoporin 93) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

NUP93 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-56758448-C-G is Benign according to our data. Variant chr16-56758448-C-G is described in ClinVar as [Benign]. Clinvar id is 1221846.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00947 (1441/152228) while in subpopulation NFE AF= 0.00945 (643/68016). AF 95% confidence interval is 0.00885. There are 33 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP93	NM_014669.5 linkuse as main transcript	c.180-90C>G		intron_variant		ENST00000308159.10
NUP93	XM_005256263.4 linkuse as main transcript	c.180-90C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP93	ENST00000308159.10 linkuse as main transcript	c.180-90C>G		intron_variant		1	NM_014669.5	P1	Q8N1F7-1

Frequencies

GnomAD3 genomes

AF:

0.00947

AC:

1441

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0646

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00945

Gnomad OTH

AF:

0.00716

GnomAD4 exome

AF:

0.0100

AC:

7859

AN:

786244

Hom.:

108

AF XY:

0.00968

AC XY:

4016

AN XY:

414908

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00308

Gnomad4 ASJ exome

AF:

0.000718

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0588

Gnomad4 NFE exome

AF:

0.00884

Gnomad4 OTH exome

AF:

0.00894

GnomAD4 genome

AF:

0.00947

AC:

1441

AN:

152228

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

846

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0646

Gnomad4 NFE

AF:

0.00945

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

DANN

Benign

0.63

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

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