Variant chr16-56748435-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_014669.5(NUP93):c.179+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,606,122 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

NUP93
NM_014669.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.553

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 16-56748435-T-G is Benign according to our data. Variant chr16-56748435-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1635121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00363 (553/152304) while in subpopulation AFR AF= 0.00835 (347/41576). AF 95% confidence interval is 0.00762. There are 1 homozygotes in gnomad4. There are 272 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP93	NM_014669.5 linkuse as main transcript	c.179+9T>G		intron_variant		ENST00000308159.10
NUP93	XM_005256263.4 linkuse as main transcript	c.179+9T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP93	ENST00000308159.10 linkuse as main transcript	c.179+9T>G		intron_variant		1	NM_014669.5	P1	Q8N1F7-1

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

556

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00213

AC:

525

AN:

246234

Hom.:

AF XY:

0.00184

AC XY:

245

AN XY:

133506

show subpopulations

Gnomad AFR exome

AF:

0.00903

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00779

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00597

GnomAD4 exome

AF:

0.00111

AC:

1618

AN:

1453818

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

776

AN XY:

721876

show subpopulations

Gnomad4 AFR exome

AF:

0.00835

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00873

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000671

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00363

AC:

553

AN:

152304

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00835

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00448

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 12

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 08, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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